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

NCT01231113 | Completed Phase 3 DMC

• 1 other identifier: version 8/DHAPPQ/MIP
• Study Type: interventional
• Target: 417
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

malaria,; pregnancy,; dihydroartemisinin-piperaquine,; efficacy,; safety,; Ghana

Outcome Measures

Primary Outcomes (1)

• PCR-corrected parasitological cure rates at days 28 and 42

  Only eligible subjects with positive falciparum rapid diagnostic test results and positive blood films on microscopy will be recruited. Filter paper blots will be prepared at recruitment as well. Blood films and filter paper blots will be repeated on days 3,7,14,28 and 42 post-first dose of treatment. PCR analysis will be conducted on only those follow-ups with positive blood films

  42-day follow-up

Secondary Outcomes (3)

• prevalence of birth defects

  assessment made 24-72 hours post-partum

• Comparative prevalence of adverse and serious adverse events

  three-monthly and at end of study

• pregnancy outcomes (spontaneous abortions, still births, preterm delivery, etc)

  quaterly from first recorded delivery and on completion

Study Arms (2)

artesunate-amodiaquine arm

ACTIVE COMPARATOR

A co-blistered pack of amodiaquine and artesunate.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: artesunate-amodiaquine

Dihydroartemisinin-piperaquine arm

EXPERIMENTAL

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

Drug: Dihydroartemisinin-piperaquine

Interventions

artesunate-amodiaquine DRUG

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

Also known as: camosunate

artesunate-amodiaquine arm

Dihydroartemisinin-piperaquine DRUG

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

Also known as: artekin

Dihydroartemisinin-piperaquine arm

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• RDT positive + microscopy confirmed P. falciparum parasitaemia. ii) Informed consent. iii) Resident within the defined 15km radius of the study center. iv) No history of antimalarial treatment in the preceding two weeks. v) Assurance of adherence to study requirements, follow-up and delivery at the hospital.
• vi) Haemoglobin ≥ 7g/dl.

You may not qualify if:

• i) Confirmed multiple gestation. ii) Severe malaria or disease likely to influence pregnancy outcome eg renal/ cardiac disease, diabetes mellitus, known pregnancy induced hypertension, known human immunodeficiency virus infection.
• iii) Known allergies to study medication. iv) Antimalarial treatment administered by a third party during the follow-up.

Sponsors & Collaborators

• Kwame Nkrumah University of Science and Technology: lead
• Malaria Capacity Development Consortium: collaborator

Study Sites (1)

St.Michael's Hospital, Pramso

Kumasi, Ashanti Region, Ghana

Location

MeSH Terms

Conditions

Malaria

Interventions

amodiaquine, artesunate drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Joseph Osarfo, MBCHB, MPH

  Malaria Capacity Development Consortium-Ghana, Department of Community Health, School of Medical Science, Kwame Nkrumah University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Harry Tagbor, PhD

  Kwame Nkrumah University of Science and Technology

  STUDY DIRECTOR

• Pascal Magnussen

  DBL-University of Copenhagen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2010
• First Posted: November 1, 2010
• Study Start: July 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: February 24, 2016

Record last verified: 2016-02

Locations

GH (1)