Development of Triple Artemisinin-based Combination Therapies

The goal of the Development of Triple Artemisinin-based Combination Therapies (DeTACT) project is to provide a solution using currently available antimalarials to contain multidrug-resistant Plasmodium falciparum malaria in the Greater Mekong Sub region, and to prevent the spread or emergence of resistance in India, Africa, and beyond. DeTACT aims to provide evidence from clinical, market and community-based research in support of a global change in policy to allow large-scale deployment of triple artemisinin-based combination therapies (TACTs) for the treatment of uncomplicated Plasmodium falciparum malaria. Switching from artemisinin-based combination therapies (ACTs) to TACTs could be one of the last available options using currently available drugs to treat multidrug-resistant falciparum malaria and prevent or delay it from spreading or emerging in areas where it is not yet present. The project is divided into seven work packages: (1) Develop two co-packaged TACTs for uncomplicated P. falciparum malaria. (2) Using these products, conduct randomised, controlled, non-inferiority trials in 13 sites in 8 African countries and 4 Asian countries to provide evidence of safety, tolerability, and efficacy of the TACTs. (3) Mathematical modelling to assess the potential of TACTs to delay the emergence and further spread of antimalarial drug resistance and the costs and benefits of introducing TACTs in countries with different levels of drug resistance, malaria transmission rates, and adherence to treatment guidelines. (4) Analyse the conceptual ethical aspects and conduct an empirical ethics/social science study addressing the ethical aspects of a change to TACTs in the African paediatric patient population. (5) A market positioning assessment based on interviews and focus group discussions with stakeholders ranging from end users to national and regional policy makers, to address the barriers and strategies to overcome these, and acceptability of changing to TACTs in Asia and Africa, which present different epidemiological settings. (6) Effective communication of the design of the study and evidence generated in order to engage with key stakeholders at an early stage. (7) Conduct a meta-analysis on harmonised individual patient-level data to compare the efficacy, safety, tolerability of TACTs versus ACTs in the general study population and in sub-groups (e.g., malnourished or undernourished children).