REACT
Trial question
What is the effect of clazosentan for the prevention of clinical deterioration due to delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
68.0% female
32.0% male
N = 406
406 patients (275 female, 131 male).
Inclusion criteria: patients with aneurysmal subarachnoid hemorrhage who had presented with thick and diffuse clot on admission CT.
Key exclusion criteria: subarachnoid hemorrhage due to causes other than a saccular aneurysm; significant bleeding following aneurysm-securing procedure; cerebral vasospasm at hospital admission; mRS score ≥ 3; hypotension refractory to treatment.
Interventions
N=202 clazosentan (at a dose of 15 mg/hr within 96 hours of aneurysmal subarachnoid hemorrhage for up to 14 days).
N=204 placebo (matching placebo within 96 hours of aneurysmal subarachnoid hemorrhage for up to 14 days).
Primary outcome
Rate of clinical deterioration due to delayed cerebral ischemia up to 14 days
15.8%
17.2%
17.2 %
12.9 %
8.6 %
4.3 %
0.0 %
Clazosentan
Placebo
No significant
difference ↔
No significant difference in the rate of clinical deterioration due to delayed cerebral ischemia up to 14 days (15.8% vs. 17.2%; RRR 7.2, 95% CI -42.6 to 39.6).
Secondary outcomes
No significant difference in clinically relevant cerebral infarcts at day 16 (7.4% vs. 11.3%; RRR 34.1, 95% CI -21.3 to 64.2).
No significant difference in risk of poor Glasgow Outcome Scale-Extended and mRS scores at week 12 post-aneurysmal subarachnoid hemorrhage (24.8% vs. 20.1%; RRR 25.4, 95% CI -10.7 to 76).
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In patients with aneurysmal subarachnoid hemorrhage who had presented with thick and diffuse clot on admission CT, clazosentan was not superior to placebo with respect to the rate of clinical deterioration due to delayed cerebral ischemia up to 14 days.
Reference
Stephan A Mayer, Nicolas Bruder, Giuseppe Citerio et al. REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2024 Aug 9;142(1):98-109.
Open reference URL