The phase 2 PIVOT trial randomised 214 patients between 5 and 50 years of age with HbSC to hydroxyurea or a placebo. Hydroxyurea was administered at a starting dose of 20 mg/kg, with 2 opportunities for dose escalation during the 12-month study period. The occurrence of dose-limiting toxicities (DLTs) was the main outcome of the study. Dr Yvonne Dei-Adomakoh (Korle-bu Teaching Hospital, Ghana) presented the findings1.
DLTs were more prevalent in participants on hydroxyurea than in those on placebo (33% vs 11%; Δ22%; 95% CI 11–34%), not meeting the non-inferiority threshold of 15%. Thrombocytopenia (19% vs 1%), neutropenia (13% vs 0%), and high haemoglobin (11% vs 11%) were the most commonly reported DLTs in the study. “All cases were asymptomatic, mild, transient, and reversible,” emphasised Dr Dei-Adomakoh.
The research team observed that a higher age at enrolment, a lower platelet count, and an increased spleen volume were associated with an elevated risk of developing DLTs. Interestingly, clinical adverse events such as vaso-occlusive pain, malaria, hospitalisation, and sickle-related events were less common among patients on hydroxyurea (IRR 0.70; 95% CI 0.48–0.92).
“Although hydroxyurea was associated with more DLTs than placebo, these events were all asymptomatic, mild, and reversible,” Dr Dei-Adomakoh summarised the findings. “Moreover, treatment with this drug led to fewer clinical adverse events than treatment with placebo. Since the PIVOT trial was not powered for efficacy, a phase 3 trial is needed to confirm the disease-modifying effect of hydroxyurea in HbSC.”
Medical writing support was provided by Robert van den Heuvel.