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Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma (TORCH)

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ClinicalTrials.gov Identifier: NCT03582293
Recruitment Status : Recruiting
First Posted : July 11, 2018
Last Update Posted : August 11, 2020
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Prof. dr. W.P. Vandertop, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

Rationale: Chronic subdural hematoma (cSDH) is a frequently occurring disease, occurring mainly in the elderly. Surgical evacuation is effective, but 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, neurological impairment (mNIHSS), the incidence of falling incidents, the mortality rate, the use of care and health-related costs (iMCQ and iPCQ), to improve cognitive functioning (MOCA), performance in activities of daily living (Barthel and Lawton-Brody), functional outcome (mRS), the level of quality of life.

Study design: Double-blind placebo-controlled multicentre randomized clinical trial.

Study population: All patients, age 50 and above, diagnosed with cSDH for whom a conservative treatment is selected as primary treatment strategy.

Intervention: The intervention group will receive oral TXA 500mg twice daily for 4 weeks, 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 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 4, 8and 12 weeks with a standard CT-scan of the head, outpatient clinic visits and 4 patient-reported questionnaires. These outpatient clinic visits are standard care; the third CT-scan, the questionnaires and extra clinical tests are extra. 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.


Condition or disease Intervention/treatment Phase
Hematoma, Subdural, Chronic Drug: Tranexamic Acid 500Mg Tablet Drug: Placebo oral capsule Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled, multicentre, randomized clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double-blind
Primary Purpose: Treatment
Official Title: Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : September 20, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Tranexamic Acid
Tranexamic acid 500mg two times a day orally for a total of 28 days
Drug: Tranexamic Acid 500Mg Tablet
orally twice daily for 28 days
Other Name: cyclokapron

Placebo Comparator: PLACEBO
Placebo capsules two times a day orally for a total of 28 days
Drug: Placebo oral capsule
Oral placebo capsule two times a day for a total of 28 days




Primary Outcome Measures :
  1. surgery for cSDH [ Time Frame: within 12 weeks after start of treatment ]
    number of patients who need to undergo surgery for cSDH


Secondary Outcome Measures :
  1. cSDH volume [ Time Frame: at four, eight and 12 weeks ]
    change in cSDH volume (in ml) on follow-up CT scan of the head

  2. neurological impairment [ Time Frame: at four, eight and 12 weeks ]
    neurological impairment measured with the modified National Institutes of Health Stroke Scale (mNIHSS) score, range 0 (normal) to 31 (severe neurological deficit)

  3. falling incidents [ Time Frame: during the 12 week study period ]
    number of falling incidents during study period

  4. cognitive functioning [ Time Frame: at four, eight and 12 weeks ]
    cognitive functioning measured with the Montreal Cognitive Assessment (MOCA) test, range 0 - 30, with a score of 26 and higher generally considered normal.

  5. performance in activities of daily living [ Time Frame: at 12 weeks ]
    performance in activities of daily measured with the Barthel Index scale (range 0-20, with lower scores indicating increased disability)

  6. functional outcome [ Time Frame: at 12 weeks ]
    functional outcome measured with the modified Rankin Scale (mRS) score, range 0 (no symptoms) to 6 (death)

  7. patient health status [ Time Frame: at 12 weeks ]
    quality of life measured with the patient-reported Short Form Health Survey questionnaire (SF-36; eight scaled scores, range 0 (maximum disability) -100 (no disability).

  8. mortality rate [ Time Frame: at 12 weeks ]
    number and percentage of deaths during study period

  9. use of care [ Time Frame: during the 12 week study period ]
    use of care measured with the Medical Consumption Questionnaire (iMCQ), which includes questions related to frequently occurring contacts with health care providers

  10. performance in activities of daily living [ Time Frame: at 12 weeks ]
    performance in activities of daily measured with the Lawton-Brody scale, range 0 (low function, dependent) to 8 (high function, independent).

  11. health-related costs [ Time Frame: during the 12 week study period ]
    health-related costs measured with the Productivity Cost Questionnaire (iPCQ), a standardized instrument including three modules for measuring and valuing productivity losses of paid work due to 1) absenteeism and 2) presenteeism and productivity losses related to 3) unpaid work.

  12. patient health status [ Time Frame: at 12 weeks ]
    quality of life measured with the five dimensional EuroQol questionnaire (EQ-5D-3L, five dimensions with each 3 levels: 1-no problems, 2-some problems, and 3-extreme problems).



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • On CT confirmed cSDH
  • Primary conservative treatment, based on clinical symptoms: Glasgow Coma Scale score >=14, mNIHSS score <=4 and a stable neurological deficit (no new, or progression of, symptoms between the assessment by the neurologist and the assessment by the neurosurgeon).

Exclusion Criteria:

Primary surgical treatment based on one or more of the following symptoms or parameters: medically intractable headache, midline shift >10mm, imminent death within 24 hours;

  • Structural causes for subdural haemorrhage, e.g. arachnoid cysts, cortical vascular malformations and a history of cranial surgery <1year;
  • Aneurysmal subarachnoid haemorrhage;
  • Active treatment for deep vein thrombosis, pulmonary embolism or cerebral thrombosis (secondary prophylaxis is not considered to be active treatment);
  • Active intravascular clotting or disseminated intravascular coagulation;
  • Known hypersensitivity or allergy to TXA or to any of the ingredients;
  • History of a blood coagulation disorder (hypercoagulability disorder);
  • History of severe impairment of renal function (eGFR <30ml/min or serum creatinine >150μmol/L);
  • History of anaemia (haemoglobin <6mmol/L);
  • History of convulsions;
  • History of inability to safely swallow oral medication.
  • Inability to obtain informed consent from the patient or legal representative (when the patient has a depressed level of consciousness as described in paragraph 11.2), including language barrier;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582293


Contacts
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Contact: William P Vandertop, MD PhD +31205669111 ext 63316 w.p.vandertop@amc.nl
Contact: Dagmar Verbaan, PhD +31205663316 d.verbaan@amc.nl

Locations
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Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1100DD
Contact: William P Vandertop, MD, PhD    +31205663316    w.p.vandertop@amc.nl   
Contact: D Verbaan    +31205663316    d.verbaan@amc.nl   
Sub-Investigator: Steven Immenga         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development
Additional Information:
Publications:

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Responsible Party: Prof. dr. W.P. Vandertop, chair Neurosurgery, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03582293    
Other Study ID Numbers: NL63794.018.18
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prof. dr. W.P. Vandertop, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Tranexamic Acid
Antifibrinolytic Agents
Additional relevant MeSH terms:
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Hematoma, Subdural
Hematoma, Subdural, Chronic
Hematoma
Hemorrhage
Pathologic Processes
Intracranial Hemorrhage, Traumatic
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Vascular Diseases
Cardiovascular Diseases
Wounds and Injuries
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants