HERCULES (thrombotic thrombocytopenic purpura)
Trial question
What is the effect of caplacizumab in patients with acquired TTP?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
69.0% female
31.0% male
N = 145
145 patients (100 female, 45 male).
Inclusion criteria: patients with acquired TTP.
Key exclusion criteria: severe ADAMTS13 deficiency, thrombotic microangiopathies unassociated with TTP, such as HUS, or congenital TTP.
Interventions
N=72 caplacizumab (10 mg IV bolus, then 10 mg SC daily during PLEX and for 30 days thereafter).
N=73 placebo (standard of care, including PLEX, with matching placebo).
Primary outcome
Platelet count normalization
90.3%
87.7%
90.3 %
67.7 %
45.1 %
22.6 %
0.0 %
Caplacizumab
Placebo
Significant
increase ▲
NNT = 38
Significant increase in platelet count normalization (90.3% vs. 87.7%; RR 1.55, 95% CI 1.09 to 2.19).
Secondary outcomes
Significant decrease in death due to TTP, recurrence, or thromboembolism (12% vs. 49%; RR 0.24, 95% CI 0.1 to 0.38).
Significant decrease in recurrence of TTP during trial (12% vs. 38%; RR 0.32, 95% CI 0.13 to 0.51).
Safety outcomes
No significant differences in bleeding-related adverse events (65% vs. 48%), death during the trial (1 vs. 3 patients).
Conclusion
In patients with acquired TTP, caplacizumab was superior to placebo with respect to platelet count normalization.
Reference
Scully M, Cataland SR, Peyvandi F et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019 Jan 24;380(4):335-346.
Open reference URL