Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma

NCT03582293 | Recruiting Phase 3 DMC

• 1 other identifier: NL63794.018.18
• Study Type: interventional
• Target: 554
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematoma, Subdural, Chronic

Keywords

Tranexamic Acid; Antifibrinolytic Agents

Outcome Measures

Primary Outcomes (1)

• surgery for cSDH

  number of patients who need to undergo surgery for cSDH

  within 12 weeks after start of treatment

Secondary Outcomes (12)

• cSDH volume

  at four, eight and 12 weeks

• neurological impairment

  at four, eight and 12 weeks

• falling incidents

  during the 12 week study period

• cognitive functioning

  at four, eight and 12 weeks

• performance in activities of daily living 1

  at 12 weeks

Study Arms (2)

Tranexamic Acid

ACTIVE COMPARATOR

Tranexamic acid 500mg two times a day orally for a total of 28 days

Drug: Tranexamic Acid 500Mg Tablet

PLACEBO

PLACEBO COMPARATOR

Placebo capsules two times a day orally for a total of 28 days

Drug: Placebo oral capsule

Interventions

Tranexamic Acid 500Mg Tablet DRUG

orally twice daily for 28 days

Also known as: Cyklokapron

Tranexamic Acid

Placebo oral capsule DRUG

Oral placebo capsule two times a day for a total of 28 days

PLACEBO

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, 1100DD, Netherlands

RECRUITING

Related Publications (27)

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Related Links

• cost of medicine
• Institute for Medical Technology Assessment
• Central Committee on Research Involving Human Subjects (CCMO) legal frameworks, codes of conduct

MeSH Terms

Conditions

Hematoma, Subdural, Chronic

Interventions

Tranexamic Acid; Tablets

Condition Hierarchy (Ancestors)

Hematoma, Subdural; 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; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematoma; Hemorrhage; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

William P Vandertop, MD PhD

CONTACT

+31205669111; w.p.vandertop@amsterdamumc.nl

Dagmar Verbaan, PhD

CONTACT

+31205663316; d.verbaan@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chair Neurosurgery

Model Details: Double-blind, placebo-controlled, multicentre, randomized clinical trial.

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: July 11, 2018
• Study Start: June 19, 2018
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): October 30, 2029
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)