About the Project
Introduction to malaria in the area
Malaria in pregnant is a public health problem in sub Saharan countries where 11 million pregnancies are exposed to malaria infection. Plasmodium falciparum in pregnant can cause adverse maternal health and poor birth outcomes. Artemisin-based Combination Therapy (ACT) used in treatment of uncomplicated Plasmodium falciparum malaria in pregnant women has the efficacy in Africa. The malaria parasite has shown resistance to Sulfadoxine-Pyrimethamin (SP) used in intermittent preventive treatment (IPTp). Other ACT as Dihydroartemisinin-Piperaquine (DP) is a potential candidate to replace SP in IPTp. Deployment of DP as IPTp would limit significantly its use as curative treatment. There is the need of other ACT to increase therapeutic options for malaria treatment in 2nd and 3rd trimester. Pyronaridine – Artesunate (PA) can be is a potential candidate.
Introduction to Pyramax®
PA (Pyramax®) is used for uncomplicated P. falciparum malaria in non-pregnant adults and children with high efficacy and good tolerability but not in pregnant women. There is no data for PA in pregnant women.
Introduction to the clinical trial
Pyrapreg is a clinical trial on malaria in pregnant women, funded by the European and Developing Countries Clinicals Trials Partership (EDCTP). It will test Pyronaridine associated to artesunate in pregnant women with malaria in 5 African countries (Gambia, Democratic Republic of the Congo, Burkina Faso, Mozambique and Mali). The main objective of this trial is to determine the safety, efficacy and pharmacokinetics of PA in pregnant women (2nd or 3rd trimester) with uncomplicated P. falciparum malaria. 1,875 pregnant women will be recruited and randomly allocated equally to the study arms (PA, AL and DP). Participating countries will share the sample size, depending on the recruitment speed of each site. This trial will provide the necessary information for an alternative, safe and effective treatment to include in the guidelines of Treatment of malaria in pregnancy, thus contributing to reducing the high burden of the disease in pregnant women.
The work plan comprises 6 work packages (WP) that will be implemented by complementary and highly experienced partners, five from Africa (Mali, Gambia, Burkina Faso, Democratic Republic of the Congo, and Mozambique) and four from Europe (The Netherlands [2 partners], Spain, and the United Kingdom, the latter with a Research Unit in The Gambia), who are all equipped to perform the tasks assigned to this group which has longstanding collaboration in research. All under leadership of WP1, the project Manager of Mali. The work will be conducted during a 5-years period.
WP 1: Coordination
WP 1 is led by Prof. Kassoum Kayentao (USSTB, Mali) and co-coordinated by Prof. Umberto d’Alessandro (Medical Research Council, MRC, The Gambia).
The coordination is the root of the project management for a total success. The overall project goal is to ensure rapid and efficient exchange of information within the consortium, excellent scientific collaboration, monitoring project progress, fulfilment of requirements related to ethical issues and scientific/financial reporting amongst project partners and to EDCTP. The objectives are:
- To establish a good financial and scientific management structure and decision-making processes across the project and through all work packages;
- To guarantee that all clinical and research activities will be compliant with GCP standards under WP2, meeting national and international ethical requirements, and that the same standard operating procedures are applied across the consortium;
- To ensure that an adequate communication system within the consortium and between the consortium and stakeholders, including EDCTP;
- To develop mechanisms to ensure identification of risks and correction measures for their mitigation.
WP2: Clinical Trial
WP2 is led by Prof. Umberto D’Alessandro (LSHTM – MRC Unit, The Gambia) and co-coordinated by Prof. Dr Hypolite Muhindo (UNIKIN, DRC).
The essential of this project focuses on this WP2 to ensure a strict adherence of clinical trials rules. It will handle the data management because it has the required expertise in all components of data management of clinical trials and epidemiological studies. The principal objective is to determine the efficacy, safety, tolerability, safety, and efficacy of PA as compared to either Artemether-Lumefantrine (AL) or Dihydroartemisinin-Piperaquine (DP) when administered to 2nd and 3rd trimester pregnant women infected with P. falciparum.
- To compare the efficacy of PA against AL or DP on the following outcomes occurring during the 63-day post-treatment active follow up and at delivery;
- To determine the safety profile of PA, AL and DP in mother and her offspring
- To explore the pharmacokinetics of pyronaridine in both HIV-infected and HIV-non infected pregnant women in the 2 countries with the highest HIV prevalence (DRC and Mozambique).
WP3: Pharmacovigilance (PV)
WP3 is led by Prof. Esperança Sevene (FM, Mozambique) and co-coordinated by Prof. Dr Halidou Tinto (CNRST-IRSS, Burkina Faso).
The principal goal is to improve PV capacity in the context of trial implementation in five malaria endemic countries by creating standardized procedures to monitor the safety of study participants including mothers and babies.
The objectives are:
- To develop safety monitoring tools flow for drug safety monitoring during the trial implementation
- To implement the tools and monitor the outcomes
- To train the study team and other health professionals on drug safety monitoring during the trial implementation
- To set-up a communication flow with study drugs providers, IRB, and the National Pharmacovigilance Centres to share the safety information.
WP4: Capacity Building
WP4 is led by Dr Petra Mens (AMC, Netherlands) and co-coordinated by Dr Mireia Piqueras (ISGlobal, Spain).
This WP elaborates the capacity building strategy of the project. The main objective is to improve clinical and research capacity in the five malaria endemic countries where the trial will be carried out. Training activities will include placental histology, GLP and GCP, ECG reading, ultrasound, molecular biology, training of 2 PhD and 5 MSc students (one from each malaria endemic country). Furthermore, this WP will support the recruiting sites in the development of ancillary studies.
The objectives are below:
- To adequately trained research, clinical and auxiliary trial’s staff complying with GCP and GLP guidelines, including adherence to SOPs.
- To train medical staff of the Project in several aspects of neonatology and paediatrics and laboratory staff on processing of placental biopsies and placenta slides reading.
- To improve and upgrade research infrastructure and technologies in the trial sites.
- To increase the research capacity of the African centres by offering post-graduate training.
WP5 is led by Prof. Dr Halidou Tinto (CNRST-IRSS/CRUN, Burkina Faso) and co-coordinated by Dr Henk Schallig (UMC-UvA, Netherlands).
The WP5 elaborates the networking plan (South-South and North-South) of the project. The main objective is to create new collaborative links and to strengthen the existing links between the institutions within consortium in order to increase the generation of evidence on maternal and child health in the most vulnerable populations which will potentially drive policy and implementation of interventions.WP4 has this objectives:
- To strengthen the existing links and to create new collaborative links between the institutions involved in this project
- To explore and improve the existing links of the members of this Consortium with international networks involved in the broader maternal, child and reproductive health community
- To promote the creation of new pathways between European and African countries to tackle poverty-related diseases affecting pregnant women and children.
- To establish a link with other institutions and stakeholders working in the field of maternal and child health.
WP6: Dissemination, Exploitation and Communications
WP6 is led by Prof. Dr Hypolite Muhindo Mavoko (UNIKIN, DRC) and co-coordinated by Dr Mireia Piqueras (ISGlobal, Spain).
The overall work package goal is to guarantee effective internal and external communication and disseminate project findings to target groups.
The objectives are:
- To design a Dissemination, Exploitation and Communication Plan.
- To implement communication tools and processes that will be essential to carry out the plan.
- To prepare electronic and hardcopy materials to disseminate the study findings to the lay public, especially to the study participants, research peers and policymakers.
- To develop a Scientific Publication Plan for the scientific dissemination of the findings of the PYRAPREG Project.
- To highlight and acknowledge the EDCTP contribution to tackle health and societal challenges.