Rationale and Design of a Randomized, Double-Blind Trial Evaluating the Efficacy of Tranexamic Acid on Hematoma Expansion and Peri-hematomal Edema in Patients with Spontaneous Intracerebral Hemorrhage within 4.5 h after Symptom Onset: The THE-ICH Trial Protocol

Abstract

Background: Hematoma expansion (HE) and peri-hematomal edema (PHE) are associated with adverse outcomes of patients with acute spontaneous intracerebral hemorrhage (sICH). Due to a lack of proven treatments, it is critical to explore novel treatments for HE and PHE to improve functional recovery after sICH.

Methods: This is a prospective, multicenter, placebo-controlled, double-blind, and randomized clinical study of approximately 2400 patients with sICH. Patients within 4.5 h of sICH onset that fulfilling the clinical criteria for diagnosis (e.g. age more than 18 years old, the Glasgow Coma Scal>7, and no planned surgery) will randomly receive either intravenous tranexamic acid (TXA) 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo (sodium chloride 0.9%). Clinical data including the ICH score and the Glasgow Coma Scale score will be collected on admission. After assessment of HE and PHE expansion, follow-up will be conducted with enrolled patients for 90 days.

Results: Primary outcome metrics are HE (defined as either >33% or >6 ml increase from baseline) and PHE expansion rate at 24 ± 3 h and 72 ± 3 h post-sICH. Secondary outcome metrics include mortality and the modified Rankin Scale on day 90 after sICH. Appropriate statistic methods will be used to evaluate the efficacy of TXA on patients with sICH within 4.5 h of symptom onset.

Conclusions: HE usually occurs within the first few hours after onset of symptoms. It is essential to evaluate the efficacy of TXA on HE within a narrow window of time. This will be the first trial to evaluate the efficacy of TXA on HE and PHE expansion in sICH patients within 4.5 h after symptom onset. This trial is registered as ChiCTR1900027065 at http://www.chictr.org.cn.

Keywords: Hematoma expansion; Intracerebral hemorrhage; Peri-hematomal edema; Tranexamic acid; Trial.