Caffeic acid tablets plus high-dose dexamethasone versus placebo plus high-dose dexamethasone in patients with newly diagnosed immune thrombocytopenia: A multicenter, double-blind, randomized, controlled, phase 2 trial.

Background: Standard initial therapy with intensive glucocorticoids requires further optimization due to high relapse rates and unsatisfying long-term outcomes in patients with primary immune thrombocytopenia (ITP). Caffeic acid (CA) has been reported to increase platelet counts in thrombocytopenia. This study investigated the efficacy and safety of CA tablets plus high-dose dexamethasone (HD-DXM) as a novel initial treatment for adults with newly diagnosed ITP.

Methods: This multicenter, double-blind, randomized, placebo-controlled trial was conducted from July 1, 2015 to February 28, 2022 in fourteen tertiary medical hospitals in China. Eligible patients aged ≥18 years with newly diagnosed, treatment-naïve primary ITP who had a baseline platelet count of <30 × 109/L were enrolled during routine outpatient visits. Participants were randomly assigned in a 1:1 ratio to receive either CA tablets (0.3 g three times daily for 12 weeks) plus HD-DXM (40 mg/day for four days, repeated with a 10-day interval) or placebo plus HD-DXM. The primary endpoint was a 24-week sustained response (SR), defined as the maintenance of a platelet count higher than 30 × 109/L, at least doubling of the baseline platelet count, and an absence of bleeding. The Chi-squared test and Kaplan-Meier method were used to compare the 24-week SR and duration of response (DOR) between groups.

Results: The intention to treat analysis included 214 patients who received at least one-dose of allocated treatments (median [Q1-Q3] age, 45 [32-55] years; 154 females [72.0%]). At week 24, 56.5% (61/108) of participants in the CA plus HD-DXM group achieved SR, which was significantly higher than 29.2% (31/106) of those in the placebo plus HD-DXM group (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.78-5.53; P <0.0001). Adding CA to HD-DXM resulted in a longer DOR than the placebo (hazard ratio 0.50; 95% CI 0.34-0.74; P = 0.00028). The most commonly observed adverse events (AEs) in both groups were gastrointestinal symptoms, anxiety or mood disorders, and fatigue, without statistically significant differences. No grade 4 or worse AEs or death occurred.

Conclusion: This study confirms CA tablets plus HD-DXM as a well-tolerated, cost-effective, and optimized initial therapy for patient with newly-diagnosed ITP to conveniently maintain platelet counts and avoid early relapse.

Trial registration: ClinicalTrials.gov. NCT02556814.