Description

This study is a prospective single-center open-label randomized controlled trial (RCT) investigating whether the administration of tranexamic acid (TXA) as an adjuvant to surgery reduces the recurrence rate of chronic subdural hematoma (CSDH) compared to surgery alone.

CSDH is a frequent neurosurgical condition, especially among elderly patients, and carries a substantial risk of recurrence after surgical evacuation. Despite standardized procedures such as burr hole drainage and postoperative irrigation with 24-hour drainage, reoperation rates remain high (5-20%). There is currently a need for adjunctive therapies to reduce recurrence and improve clinical outcomes.

Tranexamic acid is a well-established antifibrinolytic agent that inhibits plasminogen activation and stabilizes blood clots. While observational studies and limited randomized trials have suggested a potential benefit of TXA in CSDH patients, conclusive evidence remains lacking.

This trial (RATATA) randomly assigns eligible adult patients with symptomatic CSDH confirmed via CT or MRI to receive either standard surgical treatment or surgery plus adjuvant TXA. Participants in the intervention arm receive a total of 2g IV TXA (1g \<12h pre-op and 1g 12h post-op) and continue with oral TXA 500 mg twice daily for four weeks.

The primary endpoint is recurrence of the ipsilateral CSDH requiring repeat surgery within 90 days of the index operation. Recurrence is defined by both clinical deterioration and radiologically confirmed hematoma. Secondary endpoints include functional outcomes measured by the Modified Rankin Scale (mRS), health-related quality of life assessed using EQ-5D-5L, complication and adverse event rates, and 90-days mortality.

Imaging assessments will be conducted at baseline and during follow-up (post-operatively, week 4 and at surgeons´ discretion 12 weeks if indicated). The study also includes robust safety monitoring for thromboembolic and other TXA-related adverse events.

Randomization is stratified by age (≥60 vs. \<60) and gender using a computer-generated block randomization scheme. Allocation concealment is ensured via sealed opaque envelopes, and outcomes assessors for imaging and functional scores are blinded to treatment assignment.

Sample size was calculated to detect a 12% absolute reduction in recurrence (from 18% to 6%), requiring 274 patients (137 per group) with 80% power and a two-sided alpha of 0.05, accounting for a 20% loss to follow-up.

The study follows Good Clinical Practice guidelines and the Declaration of Helsinki.