NCT02909712

Cardiac Safety of Dihydroartemisinin-Piperaquine Amongst Pregnant Women in Tanzania

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 201 (actual)
• Sponsor: London School of Hygiene and Tropical Medicine · Academic / Other
• Sex: Female
• Age: 18 Years – 34 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

The trial hypothesis is that DP will increase the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, a phenomenon referred to as QT prolongation, in the study population. However, if QT prolongation is observed, it is expected to be time-limited and of no clinical consequence. The QT interval, measured in milliseconds (MS) will be corrected (QTc) to account for natural heart rate (HR) extremes. The Fridericia formula will also be used to correct (QTcF) for variation in cardio-contraction. As part of the electrocardiogram (ECG), the period from the beginning of the P wave to the beginning of the QRS complex (PR interval) will be measured, as well as the ST-segment which connects the QRS complex and the T wave. Prolongation of the QT interval will be estimated when peak drug-concentrations are most likely to be found in the peripheral blood as measured using pharmacokinetic (PK) techniques. Polymerase chain reaction (PCR) methods will be used for genetic sequencing of molecular markers (A581G) associated with malaria parasite drug resistance to SP. The rapid diagnostic test (RDT) CareStart™ will be used to screen pregnant women attending antenatal care.

Conditions

• Malaria
• Pregnancy Malaria
• Cardiotoxicity
• Cardiac Safety
• Parasitemia

Interventions

Type	Name	Description
DRUG	sulfadoxine-pyrimethamine (SP)	Women in Groups 1 and 2 will be provided the following SP regimen as directly observed therapy: 3 tablets total of 500 mg sulphadoxine and 25 mg pyrimethamine; 1 day of dosing.
DRUG	dihydroartemisinin-piperaquine (DHA-PQP)	Women in Groups 3 and 4 will be provided the following DHA-PQP regimen as directly observed therapy 3 tablets of 40 mg dihydroartemisinin and 320 mg piperaquine daily; 9 tablets total; 3 days of dosing.

Timeline

• Start date: 2016-09-01
• Primary completion: 2020-01-01
• Completion: 2020-02-01
• First posted: 2016-09-21
• Last updated: 2021-02-02

Locations

1 site across 1 country: Tanzania