Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana

Summary

Malaria in pregnancy poses enormous public health challenges, contributing to significant maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility to malaria and mediate these adverse outcomes.

The World Health Organization recommends treatment with artemisinin-combination therapy. Ghana uses quinine for malaria in first trimester pregnancies while artesunate-amodiaquine (AS-AQ) and quinine again are used in later trimesters. Recent amendments added artesunate-lumefantrine and dihydroartemisinin-piperaquine (DHA-PPQ) to the antimalarials used in the country. A high degree of safety and efficacy of DHA-PPQ is documented in several studies. DHA-PPQ, though not specified for use in pregnancy as of now, is accessible and available following its inclusion in the national malaria guidelines and may inadvertently be used to treat malaria in pregnancy. Paucity of data on DHA-PPQ use in pregnancy makes it pertinent to study its safety, tolerability and efficacy in pregnancy.

We propose an open label, randomized controlled non-inferiority comparison of DHA-PPQ and AS-AQ for treatment of uncomplicated malaria in pregnancy in second and third trimesters to assess safety, tolerability and efficacy of DHA-PPQ. Outcomes of interest include PCR-corrected cure rates at days 28 and 42, maternal haemoglobin levels at days 14 and 42, prevalence of congenital abnormalities and pregnancy wastage. Proportions and percentages will be described at 95% Confidence Intervals and compared using chi-square tests. Parametric and non-parametric tests of significance will be applied as appropriate to determine significance of differences in outcomes between the treatment groups.

Conditions

• Pregnancy Complicated by Malaria as Antepartum Condition

Interventions

DRUG

artesunate-amodiaquine

The 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days

DRUG

Dihydroartemisinin-piperaquine

a fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days

Sponsors & Collaborators

• Malaria Capacity Development Consortium

  collaborator UNKNOWN

• Kwame Nkrumah University of Science and Technology

  lead OTHER

Principal Investigators

• Joseph Osarfo, MBCHB, MPH · Malaria Capacity Development Consortium-Ghana, Department of Community Health, School of Medical Science, Kwame Nkrumah University of Science and Technology

• Harry Tagbor, PhD · Kwame Nkrumah University of Science and Technology

• Pascal Magnussen · DBL-University of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-07-31

Primary Completion

2012-12-31

Completion

2013-02-28

Countries

• Ghana

Study Locations