A pharmacokinetic randomised interventional study to optimise dihydroartemisinin-piperaquine dosing for malaria preventive treatment in Malawian infants (OPTIMAL Study) version 1.0
| dc.contributor.author | Banda, Clifford George Dr. | |
| dc.date.accessioned | 2022-10-28T12:45:49Z | |
| dc.date.available | 2022-10-28T12:45:49Z | |
| dc.date.issued | 2022-09-08 | |
| dc.description.abstract | Type of study This is an open-label randomised interventional study (with 1:1 allocation into intervention and control groups) to optimise the dosing of an antimalarial drug, dihydroartemisininpiperaquine (DP), administered with routine vaccinations, for malaria preventive treatment in infants. Problem to be studied The World Health Organisation (WHO) recommends the use of sulphadoxine-pyrimethamine (SP), administered with routine immunisation, for intermittent preventive treatment of malaria in infancy (IPTi) in areas of moderate to high transmission in sub-Saharan Africa. However, there is limited uptake of this recommendation and increasing resistance of malaria parasites to SP. Fortunately, another antimalarial drug, DP, has shown higher protective efficacy than SP. Nevertheless, there is a paucity of evidence to guide its optimal dosing when administered together with routine vaccinations in infancy. The present study seeks to define the optimal dose of DP for IPTi when administered with routine vaccinations. Overall objective The overall objective of this study is to define the optimal dose of DP for IPTi when administered with routine vaccinations Specific objectives 1. To describe age-related changes in population pharmacokinetic properties of piperaquine following partially supervised administration of IPTi-DP at four different routine immunization time points in infancy (i.e., at 10-, 14 weeks, 6 months, and 9 months of age). 2. To evaluate the association between piperaquine exposure and incidence of symptomatic and asymptomatic malaria during IPTi-DP. 3. To compare the safety and tolerability of DP following supervised administration of IPTi-DP at routine immunizations with routine immunizations alone. 4. To apply population pharmacokinetic modelling and simulation techniques to optimise the dose of piperaquine when administered as IPTi-DP Methodology 220 infants will be randomised, from 10 weeks of age, to receive DP with routine vaccines (intervention group, n=110) or standard of care; routine vaccines only (control group, n=110). They will be followed up until 12 months of age. In the intervention group, infants will contribute capillary samples for piperaquine concentrations, at different time points after administration of DP, and capillary samples to quantify malaria parasitaemia using microscopy and quantitative PCR. In the control group, infants will contribute capillary blood samples at the same time points as those in the intervention group for malaria parasitaemia over the first year of life. Additionally, the safety and tolerability of DP for IPTi with routine vaccinations will be monitored by comparing adverse events in the intervention and control groups Expected findings and their dissemination Optimised dosing regimens of DP for IPTi will be developed by applying population pharmacokinetic-pharmacodynamic modelling techniques on data obtained from: 1. Understanding age-related changes in piperaquine pharmacokinetics from infants in the intervention group. 2. Evaluating the pharmacokinetics, efficacy and safety of DP for IPTi in infants in the intervention group compared with malaria incidence and adverse events in the control group. This work will provide the much-needed evidence to inform DP dosing for IPTi when administered with routine immunisation. Additionally, it will inform future work on optimal DP dosing for malaria treatment in infants. The findings will be disseminated to study participants, in peer-reviewed scientific journals, WHO, national malaria control programs in malaria-endemic settings and ethics committees that will review and approve the study (COMREC, LSTM REC and UCT HREC). | en_US |
| dc.description.sponsorship | National Institute for Health Research (NIHR) and the Wellcome Trust through the Wellcome International Training Fellowship Scheme | en_US |
| dc.identifier.uri | http://rscarchive.kuhes.ac.mw/handle/20.500.12988/1090 | |
| dc.language.iso | en | en_US |
| dc.publisher | Kamuzu University of Health Sciences | en_US |
| dc.relation.ispartofseries | Ethics Approval;P.06/22/3663 | |
| dc.subject | Pharmacokinetic study to optimize dosing of DHA_PQ in infants | en_US |
| dc.title | A pharmacokinetic randomised interventional study to optimise dihydroartemisinin-piperaquine dosing for malaria preventive treatment in Malawian infants (OPTIMAL Study) version 1.0 | en_US |
| dc.type | Plan or blueprint | en_US |