There are 2 clinical trials
Sulfadoxine-pyrimethamine (SP) is currently recommended by the World Health Organization for use as intermittent preventive treatment against malaria in pregnancy (IPTp) in areas of moderate to high malaria transmission. However, in some locales malaria parasites have lost sensitivity to SP, compromising its protective effect. Dihydroartemisinin-piperaquine (DP) is a candidate replacement for SP. This trial is designed to confirm the cardio-safety of DP compared to SP amongst pregnant women in Tanzania.
Proportion of participants in Groups 1-4 with parasites at Days 0, 7, 14, 21 and 28 that carry the 581G and/or K540E mutations associated with SP resistance. --- K540E ---
Description: Clinical assessmentMeasure: Proportion of pregnant women treated with DHA-PQP/SP with and without asymptomatic parasitaemia who experienced clinical symptoms that could be related with a cardiac arrhythmia. Time: Measured on day 28 post-dose
Description: ElectrocardiographyMeasure: Mean QTcF/QTcB change from baseline and proportion of pregnant women treated with SP who experience changes in QT, QTcF and QTcB measurements from Day 0 pre-dose to Day 7 Time: Measured on day 7 post-dose
Description: ElectrocardiographyMeasure: Comparative analysis of the QT changes from Day 0 pre-dose to Day 7 post first dosing in pregnant women given DHA-PQP versus SP Time: Measured on day 7 post-dose
Description: ElectrocardiographyMeasure: Analysis of values and changes from baseline for the other electrocardiogram (ECG) parameters (RR, HR, PR, QRS) in pregnant women given DHA-PQP or SP Time: Measured on day 7 post-dose
Description: EfficacyMeasure: Adequate Parasitological Responses (APR) at Days 7, 14, 21 and 28 post-dose, PCR-Corrected and uncorrected Time: Measured on day 28 post-dose
Description: Parasite resistanceMeasure: Proportion of participants in Groups 1-4 with parasites at Days 0, 7, 14, 21 and 28 that carry the 581G and/or K540E mutations associated with SP resistance Time: Measured on days 28 post-dose
In Afghanistan, studies over the past 15 years have shown a high degree of Plasmodium falciparum resistance to chloroquine. In 2003 the high failure rate of chloroquine against falciparum malaria led the national malaria treatment programme to switch its recommended first line drug treatment for uncomplicated Plasmodium falciparum malaria to artemisinin-based combination therapy (ACT) in the form of Artesunate/Sulphadoxine-Pyrimethamine (AS+SP). Second line drug treatment is oral quinine (7 days). For operational reasons, prior to recent studies (manuscript in preparation) there have been no molecular data on P. falciparum SP resistance markers from within the borders of Afghanistan. These studies have revealed early evidence of increasing SP resistance (resistance polymorphisms with double DHFR & triple DHPS mutations). The aim of this study is to conduct a focused, prospective study in Kunar for monitoring of the efficacy of the AS+SP combination in this province, along with molecular studies of isolates from recruited patients.
However the investigators have obtained recent (submitted) data showing that in addition to two resistance polymorphisms in DHFR (C59R and S108N) that are well known to be at high frequency in the region, a small number of parasites in the Kunar province have three mutations (A437G, K540E and A581G) in DHPS. --- C59R --- --- S108N --- --- A437G --- --- K540E ---
Description: WHO defined ACPRMeasure: Adequate clinical and parasitological response (ACPR) Time: 42 days
Description: The incidence of any adverse event will be documented. All patients will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit.Measure: Adverse events Time: 42 days
Description: To study polymorphisms in PfDHFR, PfDHPS and copy number of PfGCH1 which are considered as markers of resistance to Sulphadoxine-pyrimethamine (SP) components.Measure: Molecular markers for antimalarial drug resistance Time: Baseline