TORCH

RATIONALE

Chronic subdural hematoma (CSDH) is a common neurological disease, occurring mainly in the elderly.

Surgical evacuation 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.

The TORCH is a randomized, placebo-controlled clinical trial which aims to prove the efficacy of TXA.

OBJECTIVES

To evaluate the efficacy of TXA to prevent surgery for CSDH.

Primary
- Number of patients requiring surgery for cSDH within 12 weeks
- Quality of life at 12 weeks, measured with the Short Form Health Survey (SF-36) questionnaire

Secondary
- Functional outcome at 4,8 and 12 weeks (modified Rankin Scale (mRS) score)
- Neurological impairment at 4, 8 and 12 weeks (modified National Institutes of Health Stroke Scale (mNIHSS) score)
- Quality of life at 4 and 8 weeks (Short Form Health Survey (SF-36) questionnaire)
- Performance in activities of daily living at 4, 8 and 12 weeks (Barthel Index scale and the Lawton-Brody scale)
- Cognitive functioning at 4, 8 and 12 weeks (Montreal Cognitive Assessment (MOCA) test)
- Quality of life at 12 weeks (five dimensional EuroQol (EQ-5D) questionnaire)
- Volume and percentage of volume reduction of cSDH at 4, 8 and 12 weeks on follow-up CT scan of the head
- Mortality at 4, 8 and 12 weeks
- Health care costs at 4, 8 and 12 weeks
- Occurrence of thromboembolic complications at 2, 4, 8 and 12 weeks

STUDY DESIGN

A double-blind, placebo-controlled, multicenter, randomized clinical trial.

Inclusion criteria
- Age ≥50 years
- On CT and/or MRI confirmed cSDH (isodense or hypodense subdural collection, uni- or bilateral)
- 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
- 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)
- Severe impairment of renal function (eGFR <30ml/min or serum creatinine >150µmol/L)
- Anaemia (haemoglobin <6g/dl);
- History of convulsions
- Pregnancy (checked with a pregnancy test only in women in their childbearing period) or breastfeeding
- Inability to obtain informed consent from the patient or legal representative (including language barrier)

INTERVENTION

Patients are randomized to either initial treatment with Tranexamic acid (TXA) or Placebo.

Intervention group: 4 weeks, oral TXA 500mg twice daily.

Control group: 4 weeks, oral placebo twice daily.

The TXA or placebo treatment is additional to standard care.

WEBSITE

www.torchstudie.nl