Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study

摘要: Summary Background Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new partner fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in with artesunate against P malaria heterogeneous population Africa. Methods did phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two Gabon, three Burkina Faso, one Benin, and two Kenya). recruited patients presenting acute monoinfection (1000–200 000 parasites per μL), central body temperature least 37·5°C or history fever past 24 h. assessed sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) adolescents (aged ≥14 years, >30 kg), 2 children 2–13 15–30 kg). randomly assigned (1:1:1:1) receive 4 mg/kg day plus mg/kg, 6 given double-blind once 3 days, monotherapy single-blind (ie, allocation was only masked from patient) days. 14 patient visits (screening, days 48 h post-treatment surveillance, visit on 7, then follow-up week until 63). The primary endpoint terms PCR-corrected cure rate reference value 90%, 10% margin, treated without major protocol deviations parasitologically confirmed safety all patients. This study registered ClinicalTrials.gov, number NCT00988507, closed. Findings Between Oct 16, 2009, Sept 22, 2010, we 326 eligible groups, last Dec 1, 2010. 284 (87%) were available per-protocol analyses. At 28, PCR-confirmed noted 68 (97%, 95% CI 90–100) 70 artesunate, 73 (99%, 93–100) 74 71 72 54 (79%, 68–88) monotherapy. dose groups met hypothesis. most common adverse events headache (30 [19%] 162 patients) worsening (23 [14%] 164 patients); occurrences similar between groups. Interpretation combined associated high rates safe tested, could be promising drug also other drugs establish generation antimalarial combinations, especially regions that have developed resistance ACTs. Funding Sanofi.