Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial View Homepage


Ontology type: schema:MedicalStudy     


Clinical Trial Info

YEARS

2018-2021

ABSTRACT

Rationale: Chronic subdural hematoma (cSDH) is a relatively frequently occurring neurological disease, occurring mainly in the elderly. Surgical evacuation of the hematoma is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery also comes with significant risks for future cognitive functioning and, therefore, loss of independency. In five small retrospective series, tranexamic acid (TXA), an antifibrinolytic drug, showed a beneficial effect on the spontaneous resolution of the hematoma and, with that, the necessity for surgery. This randomised, placebo-controlled clinical trial aims to prove the efficacy of TXA. Objectives: Primarily to evaluate the efficacy of TXA to prevent surgery for cSDH. Secondarily to evaluate the efficacy of TXA to reduce cSDH volume, to reduce neurological impairment (mNIHSS), to reduce the incidence of falling incidents, to improve cognitive functioning (MOCA), to improve performance in activities of daily living (Barthel and Lawton-Brody), to improve functional outcome (mRS), to improve the level of quality of life, to reduce the mortality rate and to reduce the use of care and health-related costs (iMCQ and iPCQ). Study design: Double-blind, placebo-controlled, multicentre, randomized clinical trial. Study population: All patients, age 50 and above, diagnosed with cSDH for which a conservative treatment is selected as primary treatment strategy. Intervention: During four weeks, the intervention group will receive oral TXA 500mg twice daily, the control group will receive a placebo twice daily. The TXA or placebo treatment is additional to standard care. Main study endpoint: The number of patients requiring surgery within 12 weeks after start of treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will use the study medication twice daily for four weeks. Follow-up is at four, eight and 12 weeks with a standard CT-scan of the head, outpatient clinic visits and four patient-reported questionnaires (at baseline and at 12 weeks). These outpatient clinic visits are standard care; the third CT-scan, the questionnaires and extra clinical tests during the visits are extra for this study. Each patient may benefit from the study if the study medication proves effective in preventing surgery for cSDH, whereas the risk of potential side effects of the medication is slight (e.g. the risk of thromboembolic events is only 0.01-0.1%). Surgery remains a possibility for those patients in whom study medication is not effective. Detailed Description 1. INTRODUCTION AND RATIONALE Chronic subdural hematoma (cSDH) is a frequently occurring neurological disease of the elderly and common in daily neurosurgical practice. It consists of an extracerebral encapsulated collection of mostly liquefied old hematoma, located between the dura and arachnoid. The original small, and often asymptomatic, haemorrhage is caused by rupture of a bridging vein after, often minor, head trauma. Due to generalized cerebral atrophy, increased venous fragility, and the more frequent use of anticoagulation therapy, older people are more at risk of developing a cSDH. During several weeks, the original hematoma is encapsulated by a membrane consisting of weak neocapillaries from where recurrent small bleedings occur. The pathophysiological mechanism is thought to be a problem in the local haemostasis due to fibrin degradation products of the original small hematoma that inhibit further haemostasis in the subdural space. Together with an osmotic draw of water, owing to its high protein content, this results in growth of the hematoma. Therefore, it usually takes several weeks for the cSDH to grow and become symptomatic. Signs and symptoms arise due to compression of brain tissue. These can be generalised, such as headaches, light-headedness, cognitive disturbances, apathy, somnolence, seizures, frequent falling and depression. Also focal deficits, such as dysphasia, motor weakness or sensory disturbances, can be symptoms of a cSDH. The current incidence of cSDH is estimated to be 15/100,000 per year. The number of patients with cSDH is expected to increase considerably in the near future due to the continuing growth of the elderly population, and the increase in the use of anticoagulation and anti-aggregation therapy. By 2030, the incidence is expected to rise up to 20/100,000 per year, thus making cSDH the most common neurosurgical condition in adults. In The Netherlands, this comes down to 3,600 new patients each year. Treatment Treatment options are conservative and surgical. Conservative treatment currently consists of a wait-and-scan policy in which the patient is regularly monitored for neurological deterioration and growth of the hematoma on follow-up imaging. Anticoagulation and antiplatelet therapy is discontinued in low-risk patients, based on individual risk-benefit assessment and the discretion of the treating physician. If the clinical condition of the patient worsens, the indication for surgical evacuation of the hematoma is re-evaluated. Spontaneous resolution of cSDH with a conservative treatment occurs in approximately 2.5% of patients, and is therefore relatively rare. Of all patients diagnosed with cSDH in The Netherlands, about 50% is primarily treated conservatively. Of these, around 75% still need an operation (own data). If the symptoms are serious or worsen over time, surgical evacuation of the hematoma is currently the designated therapy. This therapy is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery comes with significant risks for future cognitive functioning and, therefore, loss of independency. In a large series of 1205 patients, symptomatic recurrence after surgery was 9%, mortality 2% and unfavourable functional outcome 22%. Outcome measurement Studies evaluating quality of life and functional outcome with cSDH patients are scarce. The modified Rankin Scale (mRS) score is usually the only clinical outcome parameter. A literature search for quality of life in cSDH results in only two clinical studies. The first used the postoperative mRS, Barthel Index and Sickness Impact Profile as outcome measurements; the second used a pre- and postoperative Karnofsky Performance Score. Tranexamic acid As hyperfibrinolysis is thought to play a role in the liquefaction and enlargement of cSDH, pharmaceutical options to block fibrinolysis have been explored in an effort to eliminate the necessity for surgery. The use of tranexamic acid (TXA), an antifibrinolytic drug, has so far been reported in five small series. In the first retrospective series, a total of 21 patients were treated with TXA, of whom three after primary burr hole surgery. In none of these 21 patients, additional surgery was necessary. The second, a prospective pilot study in 14 patients, showed a 41% reduction of cSDH after surgery, and an additional 91% residual volume reduction on CT after 90 days, during oral TXA treatment of 650 mg per day, for a mean (SD) duration of 90 (27) days, without recurrence, re-expansion, or any complicating venous thromboembolisms. The third study, a case report series of three patients treated with 650mg TXA per day for one month after surgery for cSDH, showed no recurrences and thromboembolic complications. The fourth, a case report of one patient successfully treated primarily with TXA, was recently published, and finally, in the abstract of a Asian article, the authors conclude that administration of Gorei-San, a Japanese herbal Kampo medicine, combined with TXA has the potential to prevent recurrences of cSDH. With these limited, however promising, data no definitive conclusion can be made regarding the role of TXA in the treatment of cSDH. Therefore, a prospective study evaluating the efficacy and safety of TXA is needed. Currently, two prospective trials (the TRACS study and the TRACE study are running in an effort to answer this question. The first study, a phase 2b trial with the aim to provide preliminary data required to plan a larger phase III trial, excludes patients using anticoagulants. These patients comprise a significant portion of the cSDH patient population, and therefore, the results of the TRACS study will be difficult to extrapolate to the future care of all cSDH patients. The second study (TRACE) is a randomised, observer blinded trial, investigating the value of treating cSDH patients with TXA after surgery. This is a different patient population than proposed in the investigators' trial, in which they plan to include only patients in whom the primary treatment is conservative. Also, both trials are set up with a primary radiological outcome parameter and therefore potentially provide insufficient clinically relevant information. This phase III trial aims to investigate the efficacy and safety of TXA as an addition to a primary conservative treatment of cSDH, in an effort to prevent surgery for cSDH. Since surgical treatment under general anaesthesia and a hospital admittance of a minimum of two days is associated with significant morbidity, as described earlier, the investigators assume that preventing surgery also prevents deterioration of patients' quality of life. This trial is also the first in describing functional outcome and quality of life of cSDH patients in a prospective manner. Since the target population partially comprises patients with a depressed level of consciousness, and patients using anticoagulants and antiplatelets, these patient groups will be included in this trial as well. More... »

URL

https://clinicaltrials.gov/show/NCT03582293

Related SciGraph Publications

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/3053", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "type": "DefinedTerm"
      }
    ], 
    "description": "Rationale: Chronic subdural hematoma (cSDH) is a relatively frequently occurring neurological disease, occurring mainly in the elderly. Surgical evacuation of the hematoma is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery also comes with significant risks for future cognitive functioning and, therefore, loss of independency. In five small retrospective series, tranexamic acid (TXA), an antifibrinolytic drug, showed a beneficial effect on the spontaneous resolution of the hematoma and, with that, the necessity for surgery. This randomised, placebo-controlled clinical trial aims to prove the efficacy of TXA. Objectives: Primarily to evaluate the efficacy of TXA to prevent surgery for cSDH. Secondarily to evaluate the efficacy of TXA to reduce cSDH volume, to reduce neurological impairment (mNIHSS), to reduce the incidence of falling incidents, to improve cognitive functioning (MOCA), to improve performance in activities of daily living (Barthel and Lawton-Brody), to improve functional outcome (mRS), to improve the level of quality of life, to reduce the mortality rate and to reduce the use of care and health-related costs (iMCQ and iPCQ). Study design: Double-blind, placebo-controlled, multicentre, randomized clinical trial. Study population: All patients, age 50 and above, diagnosed with cSDH for which a conservative treatment is selected as primary treatment strategy. Intervention: During four weeks, the intervention group will receive oral TXA 500mg twice daily, the control group will receive a placebo twice daily. The TXA or placebo treatment is additional to standard care. Main study endpoint: The number of patients requiring surgery within 12 weeks after start of treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will use the study medication twice daily for four weeks. Follow-up is at four, eight and 12 weeks with a standard CT-scan of the head, outpatient clinic visits and four patient-reported questionnaires (at baseline and at 12 weeks). These outpatient clinic visits are standard care; the third CT-scan, the questionnaires and extra clinical tests during the visits are extra for this study. Each patient may benefit from the study if the study medication proves effective in preventing surgery for cSDH, whereas the risk of potential side effects of the medication is slight (e.g. the risk of thromboembolic events is only 0.01-0.1%). Surgery remains a possibility for those patients in whom study medication is not effective.\n\nDetailed Description\n1. INTRODUCTION AND RATIONALE Chronic subdural hematoma (cSDH) is a frequently occurring neurological disease of the elderly and common in daily neurosurgical practice. It consists of an extracerebral encapsulated collection of mostly liquefied old hematoma, located between the dura and arachnoid. The original small, and often asymptomatic, haemorrhage is caused by rupture of a bridging vein after, often minor, head trauma. Due to generalized cerebral atrophy, increased venous fragility, and the more frequent use of anticoagulation therapy, older people are more at risk of developing a cSDH. During several weeks, the original hematoma is encapsulated by a membrane consisting of weak neocapillaries from where recurrent small bleedings occur. The pathophysiological mechanism is thought to be a problem in the local haemostasis due to fibrin degradation products of the original small hematoma that inhibit further haemostasis in the subdural space. Together with an osmotic draw of water, owing to its high protein content, this results in growth of the hematoma. Therefore, it usually takes several weeks for the cSDH to grow and become symptomatic. Signs and symptoms arise due to compression of brain tissue. These can be generalised, such as headaches, light-headedness, cognitive disturbances, apathy, somnolence, seizures, frequent falling and depression. Also focal deficits, such as dysphasia, motor weakness or sensory disturbances, can be symptoms of a cSDH. The current incidence of cSDH is estimated to be 15/100,000 per year. The number of patients with cSDH is expected to increase considerably in the near future due to the continuing growth of the elderly population, and the increase in the use of anticoagulation and anti-aggregation therapy. By 2030, the incidence is expected to rise up to 20/100,000 per year, thus making cSDH the most common neurosurgical condition in adults. In The Netherlands, this comes down to 3,600 new patients each year. Treatment Treatment options are conservative and surgical. Conservative treatment currently consists of a wait-and-scan policy in which the patient is regularly monitored for neurological deterioration and growth of the hematoma on follow-up imaging. Anticoagulation and antiplatelet therapy is discontinued in low-risk patients, based on individual risk-benefit assessment and the discretion of the treating physician. If the clinical condition of the patient worsens, the indication for surgical evacuation of the hematoma is re-evaluated. Spontaneous resolution of cSDH with a conservative treatment occurs in approximately 2.5% of patients, and is therefore relatively rare. Of all patients diagnosed with cSDH in The Netherlands, about 50% is primarily treated conservatively. Of these, around 75% still need an operation (own data). If the symptoms are serious or worsen over time, surgical evacuation of the hematoma is currently the designated therapy. This therapy is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery comes with significant risks for future cognitive functioning and, therefore, loss of independency. In a large series of 1205 patients, symptomatic recurrence after surgery was 9%, mortality 2% and unfavourable functional outcome 22%. Outcome measurement Studies evaluating quality of life and functional outcome with cSDH patients are scarce. The modified Rankin Scale (mRS) score is usually the only clinical outcome parameter. A literature search for quality of life in cSDH results in only two clinical studies. The first used the postoperative mRS, Barthel Index and Sickness Impact Profile as outcome measurements; the second used a pre- and postoperative Karnofsky Performance Score. Tranexamic acid As hyperfibrinolysis is thought to play a role in the liquefaction and enlargement of cSDH, pharmaceutical options to block fibrinolysis have been explored in an effort to eliminate the necessity for surgery. The use of tranexamic acid (TXA), an antifibrinolytic drug, has so far been reported in five small series. In the first retrospective series, a total of 21 patients were treated with TXA, of whom three after primary burr hole surgery. In none of these 21 patients, additional surgery was necessary. The second, a prospective pilot study in 14 patients, showed a 41% reduction of cSDH after surgery, and an additional 91% residual volume reduction on CT after 90 days, during oral TXA treatment of 650 mg per day, for a mean (SD) duration of 90 (27) days, without recurrence, re-expansion, or any complicating venous thromboembolisms. The third study, a case report series of three patients treated with 650mg TXA per day for one month after surgery for cSDH, showed no recurrences and thromboembolic complications. The fourth, a case report of one patient successfully treated primarily with TXA, was recently published, and finally, in the abstract of a Asian article, the authors conclude that administration of Gorei-San, a Japanese herbal Kampo medicine, combined with TXA has the potential to prevent recurrences of cSDH. With these limited, however promising, data no definitive conclusion can be made regarding the role of TXA in the treatment of cSDH. Therefore, a prospective study evaluating the efficacy and safety of TXA is needed. Currently, two prospective trials (the TRACS study and the TRACE study are running in an effort to answer this question. The first study, a phase 2b trial with the aim to provide preliminary data required to plan a larger phase III trial, excludes patients using anticoagulants. These patients comprise a significant portion of the cSDH patient population, and therefore, the results of the TRACS study will be difficult to extrapolate to the future care of all cSDH patients. The second study (TRACE) is a randomised, observer blinded trial, investigating the value of treating cSDH patients with TXA after surgery. This is a different patient population than proposed in the investigators' trial, in which they plan to include only patients in whom the primary treatment is conservative. Also, both trials are set up with a primary radiological outcome parameter and therefore potentially provide insufficient clinically relevant information. This phase III trial aims to investigate the efficacy and safety of TXA as an addition to a primary conservative treatment of cSDH, in an effort to prevent surgery for cSDH. Since surgical treatment under general anaesthesia and a hospital admittance of a minimum of two days is associated with significant morbidity, as described earlier, the investigators assume that preventing surgery also prevents deterioration of patients' quality of life. This trial is also the first in describing functional outcome and quality of life of cSDH patients in a prospective manner. Since the target population partially comprises patients with a depressed level of consciousness, and patients using anticoagulants and antiplatelets, these patient groups will be included in this trial as well.", 
    "endDate": "2021-12-01T00:00:00Z", 
    "id": "sg:clinicaltrial.NCT03582293", 
    "keywords": [
      "tranexamic acid", 
      "operation", 
      "hematoma", 
      "Double-Blind", 
      "multicentre", 
      "randomized controlled clinical trial", 
      "rationale", 
      "neurological disease", 
      "evacuation", 
      "effective treatment", 
      "life", 
      "patient", 
      "comorbidity", 
      "General Surgery", 
      "significant risk", 
      "drug", 
      "beneficial effect", 
      "spontaneous resolution", 
      "necessity", 
      "placebo-controlled clinical trial", 
      "efficacy", 
      "neurological impairment", 
      "incidence", 
      "incident", 
      "functional outcome", 
      "MR", 
      "mortality", 
      "care", 
      "health-related cost", 
      "study design", 
      "randomized clinical trial", 
      "study population", 
      "age 50", 
      "conservative treatment", 
      "treatment strategy", 
      "intervention", 
      "intervention group", 
      "control group", 
      "placebo", 
      "placebo treatment", 
      "standard care", 
      "study endpoint", 
      "start", 
      "nature", 
      "burden", 
      "risk", 
      "participation", 
      "benefit", 
      "relatedness", 
      "study medication", 
      "follow-up", 
      "CT-scans", 
      "head", 
      "outpatient", 
      "questionnaire", 
      "baseline", 
      "clinical test", 
      "visit", 
      "potential side effect", 
      "medication", 
      "thromboembolic event", 
      "possibility", 
      "introduction", 
      "practice", 
      "collection", 
      "dura", 
      "hemorrhage", 
      "rupture", 
      "vein", 
      "Craniocerebral Trauma", 
      "cerebral atrophy", 
      "fragility", 
      "frequent use", 
      "anticoagulation therapy", 
      "old people", 
      "membrane", 
      "pathophysiological mechanism", 
      "haemostasis", 
      "degradation product", 
      "water", 
      "protein content", 
      "sign", 
      "symptom", 
      "compression", 
      "brain tissue", 
      "headache", 
      "dizziness", 
      "cognitive disturbance", 
      "apathy", 
      "somnolence", 
      "seizure", 
      "depression", 
      "deficit", 
      "aphasia", 
      "weakness", 
      "disturbance", 
      "elderly population", 
      "anticoagulation", 
      "aggregation", 
      "rise", 
      "condition", 
      "adult", 
      "Netherlands", 
      "option", 
      "policy", 
      "deterioration", 
      "antiplatelet therapy", 
      "low-risk patient", 
      "individual risk", 
      "discretion", 
      "physician", 
      "clinical condition", 
      "indication", 
      "own data", 
      "therapy", 
      "large series", 
      "Recurrence", 
      "outcome measurement", 
      "scarce", 
      "scale", 
      "score", 
      "outcome parameter", 
      "literature search", 
      "clinical study", 
      "Sickness Impact Profile", 
      "liquefaction", 
      "enlargement", 
      "pharmaceutical", 
      "fibrinolysis", 
      "small series", 
      "hole", 
      "additional surgery", 
      "pilot", 
      "reduction", 
      "volume reduction", 
      "CT", 
      "SD", 
      "duration", 
      "expansion", 
      "venous thromboembolism", 
      "third study", 
      "thromboembolic complication", 
      "article", 
      "author", 
      "Organization and Administration", 
      "San", 
      "medicine", 
      "definitive conclusion", 
      "prospective study", 
      "safety", 
      "prospective trial", 
      "TRACS", 
      "trace", 
      "first study", 
      "trial", 
      "preliminary data", 
      "Phase III trial", 
      "anticoagulant", 
      "significant portion", 
      "patient population", 
      "future care", 
      "second study", 
      "observer", 
      "different patient population", 
      "primary treatment", 
      "relevant information", 
      "surgical treatment", 
      "general anesthesia", 
      "admittance", 
      "significant morbidity", 
      "patient quality", 
      "prospective manner", 
      "Health Service Need and Demand", 
      "consciousness", 
      "antiplatelet", 
      "patient group"
    ], 
    "name": "Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial", 
    "sameAs": [
      "https://app.dimensions.ai/details/clinical_trial/NCT03582293"
    ], 
    "sdDataset": "clinical_trials", 
    "sdDatePublished": "2019-03-07T15:27", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "file:///pack/app/us_ct_data_00027.json", 
    "sponsor": [
      {
        "id": "https://www.grid.ac/institutes/grid.454758.f", 
        "type": "Organization"
      }, 
      {
        "id": "https://www.grid.ac/institutes/grid.5650.6", 
        "type": "Organization"
      }, 
      {
        "id": "https://www.grid.ac/institutes/grid.438427.e", 
        "type": "Organization"
      }
    ], 
    "startDate": "2018-06-01T00:00:00Z", 
    "subjectOf": [
      {
        "id": "https://doi.org/10.1056/nejmoa1606424", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005102939"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.beth.2006.05.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005871597"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jval.2016.01.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009435949"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0090-3019(97)00188-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012712396"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/jth.12654", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015176458"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1745-6215-14-143", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024039705", 
          "https://doi.org/10.1186/1745-6215-14-143"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.clineuro.2014.05.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024817127"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10143-004-0337-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025058666", 
          "https://doi.org/10.1007/s10143-004-0337-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s13760-012-0130-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029060586", 
          "https://doi.org/10.1007/s13760-012-0130-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13063-016-1358-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030712953", 
          "https://doi.org/10.1186/s13063-016-1358-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/pmj.78.916.71", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032562505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/2325957416680294", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032993529"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jocn.2009.11.023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033357341"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1468-1331.2012.03768.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037579913"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/scs.0000000000000814", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043534118"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(10)60835-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044378391"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.seizure.2016.02.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045468077"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.wneu.2016.03.062", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052626168"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1055/s-0036-1584212", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1057362937"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3171/2013.3.jns122162", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071078684"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3171/2014.9.jns141550", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071080728"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3171/2016.8.jns16134", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071082808"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1055/s-0037-1616122", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1074870266"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075273698", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078639872", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.23736/s0390-5616.17.04103-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092003646"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "type": "MedicalStudy", 
    "url": "https://clinicaltrials.gov/show/NCT03582293"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/clinicaltrial.NCT03582293'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/clinicaltrial.NCT03582293'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/clinicaltrial.NCT03582293'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/clinicaltrial.NCT03582293'


 

This table displays all metadata directly associated to this object as RDF triples.

279 TRIPLES      16 PREDICATES      219 URIs      185 LITERALS      1 BLANK NODES

Subject Predicate Object
1 sg:clinicaltrial.NCT03582293 schema:about anzsrc-for:3053
2 schema:description Rationale: Chronic subdural hematoma (cSDH) is a relatively frequently occurring neurological disease, occurring mainly in the elderly. Surgical evacuation of the hematoma is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery also comes with significant risks for future cognitive functioning and, therefore, loss of independency. In five small retrospective series, tranexamic acid (TXA), an antifibrinolytic drug, showed a beneficial effect on the spontaneous resolution of the hematoma and, with that, the necessity for surgery. This randomised, placebo-controlled clinical trial aims to prove the efficacy of TXA. Objectives: Primarily to evaluate the efficacy of TXA to prevent surgery for cSDH. Secondarily to evaluate the efficacy of TXA to reduce cSDH volume, to reduce neurological impairment (mNIHSS), to reduce the incidence of falling incidents, to improve cognitive functioning (MOCA), to improve performance in activities of daily living (Barthel and Lawton-Brody), to improve functional outcome (mRS), to improve the level of quality of life, to reduce the mortality rate and to reduce the use of care and health-related costs (iMCQ and iPCQ). Study design: Double-blind, placebo-controlled, multicentre, randomized clinical trial. Study population: All patients, age 50 and above, diagnosed with cSDH for which a conservative treatment is selected as primary treatment strategy. Intervention: During four weeks, the intervention group will receive oral TXA 500mg twice daily, the control group will receive a placebo twice daily. The TXA or placebo treatment is additional to standard care. Main study endpoint: The number of patients requiring surgery within 12 weeks after start of treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will use the study medication twice daily for four weeks. Follow-up is at four, eight and 12 weeks with a standard CT-scan of the head, outpatient clinic visits and four patient-reported questionnaires (at baseline and at 12 weeks). These outpatient clinic visits are standard care; the third CT-scan, the questionnaires and extra clinical tests during the visits are extra for this study. Each patient may benefit from the study if the study medication proves effective in preventing surgery for cSDH, whereas the risk of potential side effects of the medication is slight (e.g. the risk of thromboembolic events is only 0.01-0.1%). Surgery remains a possibility for those patients in whom study medication is not effective. Detailed Description 1. INTRODUCTION AND RATIONALE Chronic subdural hematoma (cSDH) is a frequently occurring neurological disease of the elderly and common in daily neurosurgical practice. It consists of an extracerebral encapsulated collection of mostly liquefied old hematoma, located between the dura and arachnoid. The original small, and often asymptomatic, haemorrhage is caused by rupture of a bridging vein after, often minor, head trauma. Due to generalized cerebral atrophy, increased venous fragility, and the more frequent use of anticoagulation therapy, older people are more at risk of developing a cSDH. During several weeks, the original hematoma is encapsulated by a membrane consisting of weak neocapillaries from where recurrent small bleedings occur. The pathophysiological mechanism is thought to be a problem in the local haemostasis due to fibrin degradation products of the original small hematoma that inhibit further haemostasis in the subdural space. Together with an osmotic draw of water, owing to its high protein content, this results in growth of the hematoma. Therefore, it usually takes several weeks for the cSDH to grow and become symptomatic. Signs and symptoms arise due to compression of brain tissue. These can be generalised, such as headaches, light-headedness, cognitive disturbances, apathy, somnolence, seizures, frequent falling and depression. Also focal deficits, such as dysphasia, motor weakness or sensory disturbances, can be symptoms of a cSDH. The current incidence of cSDH is estimated to be 15/100,000 per year. The number of patients with cSDH is expected to increase considerably in the near future due to the continuing growth of the elderly population, and the increase in the use of anticoagulation and anti-aggregation therapy. By 2030, the incidence is expected to rise up to 20/100,000 per year, thus making cSDH the most common neurosurgical condition in adults. In The Netherlands, this comes down to 3,600 new patients each year. Treatment Treatment options are conservative and surgical. Conservative treatment currently consists of a wait-and-scan policy in which the patient is regularly monitored for neurological deterioration and growth of the hematoma on follow-up imaging. Anticoagulation and antiplatelet therapy is discontinued in low-risk patients, based on individual risk-benefit assessment and the discretion of the treating physician. If the clinical condition of the patient worsens, the indication for surgical evacuation of the hematoma is re-evaluated. Spontaneous resolution of cSDH with a conservative treatment occurs in approximately 2.5% of patients, and is therefore relatively rare. Of all patients diagnosed with cSDH in The Netherlands, about 50% is primarily treated conservatively. Of these, around 75% still need an operation (own data). If the symptoms are serious or worsen over time, surgical evacuation of the hematoma is currently the designated therapy. This therapy is an effective treatment, but is also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery comes with significant risks for future cognitive functioning and, therefore, loss of independency. In a large series of 1205 patients, symptomatic recurrence after surgery was 9%, mortality 2% and unfavourable functional outcome 22%. Outcome measurement Studies evaluating quality of life and functional outcome with cSDH patients are scarce. The modified Rankin Scale (mRS) score is usually the only clinical outcome parameter. A literature search for quality of life in cSDH results in only two clinical studies. The first used the postoperative mRS, Barthel Index and Sickness Impact Profile as outcome measurements; the second used a pre- and postoperative Karnofsky Performance Score. Tranexamic acid As hyperfibrinolysis is thought to play a role in the liquefaction and enlargement of cSDH, pharmaceutical options to block fibrinolysis have been explored in an effort to eliminate the necessity for surgery. The use of tranexamic acid (TXA), an antifibrinolytic drug, has so far been reported in five small series. In the first retrospective series, a total of 21 patients were treated with TXA, of whom three after primary burr hole surgery. In none of these 21 patients, additional surgery was necessary. The second, a prospective pilot study in 14 patients, showed a 41% reduction of cSDH after surgery, and an additional 91% residual volume reduction on CT after 90 days, during oral TXA treatment of 650 mg per day, for a mean (SD) duration of 90 (27) days, without recurrence, re-expansion, or any complicating venous thromboembolisms. The third study, a case report series of three patients treated with 650mg TXA per day for one month after surgery for cSDH, showed no recurrences and thromboembolic complications. The fourth, a case report of one patient successfully treated primarily with TXA, was recently published, and finally, in the abstract of a Asian article, the authors conclude that administration of Gorei-San, a Japanese herbal Kampo medicine, combined with TXA has the potential to prevent recurrences of cSDH. With these limited, however promising, data no definitive conclusion can be made regarding the role of TXA in the treatment of cSDH. Therefore, a prospective study evaluating the efficacy and safety of TXA is needed. Currently, two prospective trials (the TRACS study and the TRACE study are running in an effort to answer this question. The first study, a phase 2b trial with the aim to provide preliminary data required to plan a larger phase III trial, excludes patients using anticoagulants. These patients comprise a significant portion of the cSDH patient population, and therefore, the results of the TRACS study will be difficult to extrapolate to the future care of all cSDH patients. The second study (TRACE) is a randomised, observer blinded trial, investigating the value of treating cSDH patients with TXA after surgery. This is a different patient population than proposed in the investigators' trial, in which they plan to include only patients in whom the primary treatment is conservative. Also, both trials are set up with a primary radiological outcome parameter and therefore potentially provide insufficient clinically relevant information. This phase III trial aims to investigate the efficacy and safety of TXA as an addition to a primary conservative treatment of cSDH, in an effort to prevent surgery for cSDH. Since surgical treatment under general anaesthesia and a hospital admittance of a minimum of two days is associated with significant morbidity, as described earlier, the investigators assume that preventing surgery also prevents deterioration of patients' quality of life. This trial is also the first in describing functional outcome and quality of life of cSDH patients in a prospective manner. Since the target population partially comprises patients with a depressed level of consciousness, and patients using anticoagulants and antiplatelets, these patient groups will be included in this trial as well.
3 schema:endDate 2021-12-01T00:00:00Z
4 schema:keywords CT
5 CT-scans
6 Craniocerebral Trauma
7 Double-Blind
8 General Surgery
9 Health Service Need and Demand
10 MR
11 Netherlands
12 Organization and Administration
13 Phase III trial
14 Recurrence
15 SD
16 San
17 Sickness Impact Profile
18 TRACS
19 additional surgery
20 admittance
21 adult
22 age 50
23 aggregation
24 anticoagulant
25 anticoagulation
26 anticoagulation therapy
27 antiplatelet
28 antiplatelet therapy
29 apathy
30 aphasia
31 article
32 author
33 baseline
34 beneficial effect
35 benefit
36 brain tissue
37 burden
38 care
39 cerebral atrophy
40 clinical condition
41 clinical study
42 clinical test
43 cognitive disturbance
44 collection
45 comorbidity
46 compression
47 condition
48 consciousness
49 conservative treatment
50 control group
51 deficit
52 definitive conclusion
53 degradation product
54 depression
55 deterioration
56 different patient population
57 discretion
58 disturbance
59 dizziness
60 drug
61 dura
62 duration
63 effective treatment
64 efficacy
65 elderly population
66 enlargement
67 evacuation
68 expansion
69 fibrinolysis
70 first study
71 follow-up
72 fragility
73 frequent use
74 functional outcome
75 future care
76 general anesthesia
77 haemostasis
78 head
79 headache
80 health-related cost
81 hematoma
82 hemorrhage
83 hole
84 incidence
85 incident
86 indication
87 individual risk
88 intervention
89 intervention group
90 introduction
91 large series
92 life
93 liquefaction
94 literature search
95 low-risk patient
96 medication
97 medicine
98 membrane
99 mortality
100 multicentre
101 nature
102 necessity
103 neurological disease
104 neurological impairment
105 observer
106 old people
107 operation
108 option
109 outcome measurement
110 outcome parameter
111 outpatient
112 own data
113 participation
114 pathophysiological mechanism
115 patient
116 patient group
117 patient population
118 patient quality
119 pharmaceutical
120 physician
121 pilot
122 placebo
123 placebo treatment
124 placebo-controlled clinical trial
125 policy
126 possibility
127 potential side effect
128 practice
129 preliminary data
130 primary treatment
131 prospective manner
132 prospective study
133 prospective trial
134 protein content
135 questionnaire
136 randomized clinical trial
137 randomized controlled clinical trial
138 rationale
139 reduction
140 relatedness
141 relevant information
142 rise
143 risk
144 rupture
145 safety
146 scale
147 scarce
148 score
149 second study
150 seizure
151 sign
152 significant morbidity
153 significant portion
154 significant risk
155 small series
156 somnolence
157 spontaneous resolution
158 standard care
159 start
160 study design
161 study endpoint
162 study medication
163 study population
164 surgical treatment
165 symptom
166 therapy
167 third study
168 thromboembolic complication
169 thromboembolic event
170 trace
171 tranexamic acid
172 treatment strategy
173 trial
174 vein
175 venous thromboembolism
176 visit
177 volume reduction
178 water
179 weakness
180 schema:name Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial
181 schema:sameAs https://app.dimensions.ai/details/clinical_trial/NCT03582293
182 schema:sdDatePublished 2019-03-07T15:27
183 schema:sdLicense https://scigraph.springernature.com/explorer/license/
184 schema:sdPublisher N0e84a2c6279d4b3db65805ca20fd266b
185 schema:sponsor https://www.grid.ac/institutes/grid.438427.e
186 https://www.grid.ac/institutes/grid.454758.f
187 https://www.grid.ac/institutes/grid.5650.6
188 schema:startDate 2018-06-01T00:00:00Z
189 schema:subjectOf sg:pub.10.1007/s10143-004-0337-6
190 sg:pub.10.1007/s13760-012-0130-1
191 sg:pub.10.1186/1745-6215-14-143
192 sg:pub.10.1186/s13063-016-1358-5
193 https://app.dimensions.ai/details/publication/pub.1075273698
194 https://app.dimensions.ai/details/publication/pub.1078639872
195 https://doi.org/10.1016/j.beth.2006.05.002
196 https://doi.org/10.1016/j.clineuro.2014.05.003
197 https://doi.org/10.1016/j.jocn.2009.11.023
198 https://doi.org/10.1016/j.jval.2016.01.003
199 https://doi.org/10.1016/j.seizure.2016.02.011
200 https://doi.org/10.1016/j.wneu.2016.03.062
201 https://doi.org/10.1016/s0090-3019(97)00188-2
202 https://doi.org/10.1016/s0140-6736(10)60835-5
203 https://doi.org/10.1055/s-0036-1584212
204 https://doi.org/10.1055/s-0037-1616122
205 https://doi.org/10.1056/nejmoa1606424
206 https://doi.org/10.1097/scs.0000000000000814
207 https://doi.org/10.1111/j.1468-1331.2012.03768.x
208 https://doi.org/10.1111/jth.12654
209 https://doi.org/10.1136/pmj.78.916.71
210 https://doi.org/10.1177/2325957416680294
211 https://doi.org/10.23736/s0390-5616.17.04103-0
212 https://doi.org/10.3171/2013.3.jns122162
213 https://doi.org/10.3171/2014.9.jns141550
214 https://doi.org/10.3171/2016.8.jns16134
215 schema:url https://clinicaltrials.gov/show/NCT03582293
216 sgo:license sg:explorer/license/
217 sgo:sdDataset clinical_trials
218 rdf:type schema:MedicalStudy
219 N0e84a2c6279d4b3db65805ca20fd266b schema:name Springer Nature - SN SciGraph project
220 rdf:type schema:Organization
221 anzsrc-for:3053 schema:inDefinedTermSet anzsrc-for:
222 rdf:type schema:DefinedTerm
223 sg:pub.10.1007/s10143-004-0337-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025058666
224 https://doi.org/10.1007/s10143-004-0337-6
225 rdf:type schema:CreativeWork
226 sg:pub.10.1007/s13760-012-0130-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029060586
227 https://doi.org/10.1007/s13760-012-0130-1
228 rdf:type schema:CreativeWork
229 sg:pub.10.1186/1745-6215-14-143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024039705
230 https://doi.org/10.1186/1745-6215-14-143
231 rdf:type schema:CreativeWork
232 sg:pub.10.1186/s13063-016-1358-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030712953
233 https://doi.org/10.1186/s13063-016-1358-5
234 rdf:type schema:CreativeWork
235 https://app.dimensions.ai/details/publication/pub.1075273698 schema:CreativeWork
236 https://app.dimensions.ai/details/publication/pub.1078639872 schema:CreativeWork
237 https://doi.org/10.1016/j.beth.2006.05.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005871597
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1016/j.clineuro.2014.05.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024817127
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1016/j.jocn.2009.11.023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033357341
242 rdf:type schema:CreativeWork
243 https://doi.org/10.1016/j.jval.2016.01.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009435949
244 rdf:type schema:CreativeWork
245 https://doi.org/10.1016/j.seizure.2016.02.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045468077
246 rdf:type schema:CreativeWork
247 https://doi.org/10.1016/j.wneu.2016.03.062 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052626168
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1016/s0090-3019(97)00188-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012712396
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1016/s0140-6736(10)60835-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044378391
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1055/s-0036-1584212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1057362937
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1055/s-0037-1616122 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074870266
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1056/nejmoa1606424 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005102939
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1097/scs.0000000000000814 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043534118
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1111/j.1468-1331.2012.03768.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1037579913
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1111/jth.12654 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015176458
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1136/pmj.78.916.71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032562505
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1177/2325957416680294 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032993529
268 rdf:type schema:CreativeWork
269 https://doi.org/10.23736/s0390-5616.17.04103-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092003646
270 rdf:type schema:CreativeWork
271 https://doi.org/10.3171/2013.3.jns122162 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071078684
272 rdf:type schema:CreativeWork
273 https://doi.org/10.3171/2014.9.jns141550 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071080728
274 rdf:type schema:CreativeWork
275 https://doi.org/10.3171/2016.8.jns16134 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071082808
276 rdf:type schema:CreativeWork
277 https://www.grid.ac/institutes/grid.438427.e schema:Organization
278 https://www.grid.ac/institutes/grid.454758.f schema:Organization
279 https://www.grid.ac/institutes/grid.5650.6 schema:Organization
 




Preview window. Press ESC to close (or click here)


...