Tranexamic Acid and Tocilizumab as Adjuvant Therapy to Chronic Subdural Hematoma Surgery: A Randomized Controlled Trial.

BACKGROUND AND

OBJECTIVES

Chronic subdural hematoma (CSDH) recurs in 10% to 20% of patients after surgical evacuation, underscoring the need for adjuvant pharmacotherapies targeting the underlying pathophysiology. Tranexamic acid (TXA), an antifibrinolytic agent, and tocilizumab (TCZ), an anti-inflammatory agent, represent promising therapeutic candidates.The objective was to evaluate the efficacy of adjuvant TXA monotherapy and combined TXA-TCZ therapy after CSDH surgery in reducing recurrence and improving clinical outcomes.

METHODS

In this single-center, open-label, randomized controlled trial, adults 55 years and older undergoing burr hole evacuation for CSDH were randomized to TXA alone (loading dose followed by 500 mg orally twice daily), TXA plus subcutaneous TCZ (162 mg weekly for 4 weeks), or surgery alone (control). The primary end point was symptomatic recurrence requiring reoperation within 6 months. Secondary end points included hematoma volume reduction, time to radiographic resolution, functional outcome assessed using Barthel index, and safety.

RESULTS

Of 382 randomized participants (129 TXA, 127 TXA-TCZ, 126 control), 375 completed follow-up. Recurrence rates were 0.8% (n = 1) for TXA, 0% (n = 0) for TXA-TCZ, and 6.3% (n = 8) for control. Both TXA (absolute risk reduction 5.6%, 95% CI 1.3%-11.4%, P = .018) and TXA-TCZ (6.3%, 95% CI 3.2%-12.0%, P = .003) significantly reduced recurrence compared with control. Although underpowered for direct comparisons between active treatment arms, exploratory analyses suggested more rapid radiographic resolution and improved functional recovery with TXA-TCZ. Overall serious adverse event (AE) rates were similar across groups; however, surgery- or therapy-related infectious AEs were numerically more frequent with TXA-TCZ (6.3%) than TXA alone (1.6%; odds ratio 4.25, 95% CI 0.82-41.89; P = .059).

CONCLUSION

Adjuvant TXA, alone or combined with TCZ, significantly reduced postoperative CSDH recurrence without increasing overall AEs. Exploratory analyses suggested additional radiographic and functional benefits with TXA-TCZ although infectious complications were numerically more frequent. Larger adequately powered trials are warranted to define the risk-benefit profile of combined TXA-TCZ therapy.