📋 Tender Overview
Safety Of Antimalarials In The First Trimester: An Adaptive Platform Trial
Effective And Acceptably Safe Malaria Treatment In The First Trimester Of Pregnancymalaria During Early Pregnancy Can Have Severe Consequences, Yet Clinical Trials Often Exclude First-Trimester Pregnancies, Resulting In The Withholding Of New And Effective Antimalarials. While Artemether-Lumefantrine (Al) Is Recommended As The First-Line Treatment For Uncomplicated Malaria In The First Trimester, There Remains Insufficient Data On The Benefit-Harm Profile Of Other Artemisinin-Based Combination Therapies (Acts). To Address This Gap, The Eu-Funded Safire Project Will Conduct A Phase Iiib, Non-Inferiority, Bayesian Adaptive Randomised Platform Trial Comparing Acts For Which No Safety Signal Was Detected In Preclinical Studies Or Observational Studies And Al. This Research Will Offer Crucial Information On The Safety And Efficacy Of Alternatives To Al For Treating Malaria In The First Trimester.
Funded Under
Health
Total Cost
€ 5 191 431,44
Eu Contribution
€ 5 191 431,44
Coordinated By
Stichting Amsterdam Umc
Netherlands
Start Date
1 June 2024
End Date
30 November 2028
Objective
Background: Malaria in pregnancy can have devastating consequences, particularly in early pregnancy. Effective treatment in the first trimester can significantly improve maternal and pregnancy outcomes. However, first-trimester pregnancies are generally excluded from clinical trials resulting in new and effective antimalarials being withheld from use in early pregnancy. WHO updated its guidelines in 2022 from quinine to artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in the first trimester. However, there are insufficient data on the benefit-harm of other widely used artemisinin-based combination therapies.
Objectives: 1) To generate robust evidence on the safety, tolerability, and efficacy of antimalarials for the treatment of uncomplicated P. falciparum malaria in the first trimester. 2) Translate research findings into treatment guidelines and clinical practice.
Study design: a) Phase IIIb, non-inferiority, Bayesian adaptive randomised platform trial comparing pyronaridine-artesunate (PA) and AL in Burkina Faso, Kenya and Mali. Primary outcome: Safety. Secondary outcomes: efficacy and tolerability. b) Formative research to inform innovative trial recruitment and retention strategies, c) Acceptability and feasibility to assess values and preferences of antimalarials during early pregnancy, d) implementation research to explore factors affecting implementation of AL in the first trimester to inform translation strategies, and e) cost-effectiveness of PA vs AL.
Impact: The trial will provide critical information on the safety and efficacy of alternatives to AL for treatment in the first trimester, benefiting settings where AL is not used and aligning with WHO's strategy of multiple first-line therapies against antimalarial drug resistance. Resul
