A Controlled Trial for Preventing Priapism in Sickle Cell Anemia: Hydroxyurea plus Placebo vs Hydroxyurea plus Tadalafil.

Abstract

Recurrent ischemic priapism is a common complication of sickle cell anemia (SCA) and is associated with devastating physical and psychosocial consequences. All previous trials for priapism prevention have failed to demonstrate clear efficacy. We conducted a randomized, controlled, double-blind phase 2 feasibility trial comparing fixed moderate-dose hydroxyurea plus placebo (usual care arm) versus fixed moderate-dose hydroxyurea plus tadalafil (experimental arm) in 64 men (18- 40 years) with at least three episodes of SCA-related priapism in the past 12 months. Priapism data were obtained via daily text messages to the participants. The trial's primary outcome measures were 100% recruitment, 98.4% retention, and 93.5% adherence rates. Over a median of 10 months (IQR: 3-12), 2.5 and 3.02 priapism events per participant-month were recorded in the usual care and the experimental arms, with an incidence rate ratio of 0.8; 95% CI: 0.3 -1.9; p= 0.654. Serious adverse events (p=0.999) and hospitalizations (p=0.289) were similar in both arms. Sperm concentration, motility, and normal morphology significantly decreased on hydroxyurea therapy but recovered to pre-hydroxyurea levels three months after therapy cessation. Post-hoc, single-arm, pre- and post-analysis comparing the priapism rate in the treatment phase to pre-randomization showed a 58.3% priapism incidence rate reduction in the usual care arm (5.9 to 2.5 events per month; difference 3.4, 95% CI: 1.1 - 5.8; p=0.005]) and 66.3% priapism reduction in the experimental arm (8.9 to 3.02 events per month; difference 5.9; 95% CI: 3.4 - 8.5; p<0.001]). A randomized controlled trial for priapism prevention is feasible in men with SCA. (NCT05142254).