Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy (MiPPAD)

March 19, 2014 updated by: Hospital Clinic of Barcelona

Evaluation of the Safety and Efficacy of Mefloquine as Intermittent Preventive Treatment of Malaria in Pregnancy

The study aims at comparing the safety, tolerability and efficacy of Mefloquine (MQ) to Sulfadoxine-Pyrimethamine (SP) as Interment Preventive Treatment in pregnancy (IPTp) for the prevention of malaria effects on the mother and her infant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The current recommendation by the World Health Organization (WHO) to prevent malaria infection in pregnancy in areas of stable malaria transmission relies on:

  • Prompt and effective case management of malaria illness
  • The use of intermittent preventive treatment (IPTp) with at least 2 treatment doses of sulfadoxine-pyrimethamine (SP) and
  • The use of insecticide treated nets (ITNs)

However, the spread of parasite resistance to SP, particularly in eastern Africa, and the significant overlap in some regions of malaria transmission and high prevalence of HIV infection, have raised concerns about the medium and long-term use of SP for IPTp.

HIV infection increases susceptibility to malaria and may reduce the efficacy of interventions. The evaluation of alternative antimalarials for IPTp is thus urgently needed also involving HIV infected women.

Of all the current available alternative antimalarial drugs, mefloquine (MQ) is the one that offers the most comparative advantages to SP.

A randomized multicenter trial will be conducted in 4 sites in Africa (Benin, Gabon, Tanzania and Mozambique) in order to compare the safety and efficacy of SP versus MQ as IPTp in the context of ITNs. In addition, MQ tolerability will be also evaluated by comparing the administration of MQ as a single intake with its administration as split dose in two days. In total 4716 pregnant women will be enrolled at the antenatal clinic (ANC) and will be followed until the infant is one year old.

Besides, in those countries where HIV prevalence in pregnant women is > 10%, MQ-IPTp will be compared to Placebo-IPTp in HIV infected pregnant women receiving cotrimoxazole (CTX) prophylaxis. This trial will be double blinded and will be carried out in Kenya, Tanzania and Mozambique. It will involve 1070 pregnant women that will be followed until the infant is 2 months old.

Study Type

Interventional

Enrollment (Actual)

5820

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Benin
      • Allada, Benin
        • Faculté des Sciences de la Santé (FSS), Université d'Abomey Calavi
  • Gabon
      • Lambaréné, Gabon
        • Medical Rsearch Unit (MRU), Albert Schweitzer Hospital
  • Kenya
      • Kisumu, Kenya
        • Kenya Medical Research Institute (KEMRI)/ CDC
  • Mozambique
    • Maputo
      • Manhiça, Maputo, Mozambique
        • Centro de Investigação em Saúde da Manhiça (CISM)
  • Tanzania
      • Dodoma, Tanzania
        • Ifakara Health Institute (IHI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Trial 1:

  • Permanent resident in the area
  • Gestational age at the first antenatal visit ≤ 28 weeks
  • Signed informed consent
  • Agreement to deliver in the study site's maternity(ies) wards

Trial 2:

  • Permanent resident in the area.
  • Gestational age at the first antenatal visit ≤ 28 weeks
  • HIV seropositive (after voluntary counseling and testing)
  • Indication to receive CTX prophylaxis (according to the national guidelines)
  • Signed informed consent
  • Agreement to deliver in the study site's maternity(ies) wards.

Exclusion Criteria:

Trial 1:

  • Residence outside the study area or planning to move out in the following 18 months from enrollment
  • Gestational age at the first antenatal visit > 28 weeks of pregnancy
  • Known history of allergy to sulfa drugs or mefloquine
  • Known history of severe renal, hepatic, psychiatric or neurological disease
  • MQ or halofantrine treatment in the preceding 4 weeks
  • HIV infection
  • Participating in other studies

Trial 2:

  • Residence outside the study area or planning to move out in the following 10 months from enrollment
  • Gestational age at the first antenatal visit > 28 weeks of pregnancy
  • Known history of allergy to CTX or MQ
  • Known history of severe renal, hepatic, psychiatric or neurological disease
  • MQ or halofantrine treatment in the preceding 4 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Trial 1: IPTp-SP+LLITNs
HIV-negative pregnant women receiving 2 doses of IPTp (500mg of sulfadoxine and 25 mg of pyrimethamine) in the context of long lasting Insecticide Treated Nets (LLITNs)
Drug: Sulphadoxine-pyrimethamine
SP oral administration (500mg sulphadoxine and 25mg pyrimethamine) as IPTp at the 1st and 2nd Antenatal Clinic visit
EXPERIMENTAL: Trial 1: IPTp-MQ (full dose) + LLITNs
HIV-negative pregnant women receiving 2 full doses of IPTp (15 mg/Kg) in the context of long lasting Insecticide Treated Nets (LLITNs)
Drug: Mefloquine (full dose)
MQ oral administration (15 mg/Kg) on 1 day at the 1st and 2nd Antenatal Clinic visit as IPTp
EXPERIMENTAL: Trial 1: IPTp-MQ (split dose)+LLITNs
HIV-negative pregnant women receiving 2 doses of MQ as IPTp split dose over 2 days (15mg/kg) in the context of long lasting Insecticide Treated Nets (LLITNs
Drug: Mefloquine (split dose)
MQ oral administration (15 mg/kg) split dose over 2 days at the 1st and 2nd ANC visit as IPTp
EXPERIMENTAL: Trial 2: CTX+IPTp-Placebo+LLITNs
HIV-positive pregnant women receiving 3 doses of IPTp (placebo) in the context of long lasting Insecticide Treated Nets (LLITNs)
Drug: placebo
MQ-placebo oral administration at the 1st, 2nd and 3rd Antenatal Clinic visit as IPTp
EXPERIMENTAL: Trial 2: CTX + IPTp-MQ+ LLITNs
HIV-positive pregnant women receiving 3 doses of IPTp (15 mg/Kg) in the context of long lasting Insecticide Treated Nets (LLITNs)
Drug: mefloquine
MQ oral administration (15 mg/Kg) at the 1st and 2nd Antenatal Clinic visit as IPTp

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Trial 1 (IPTp MQ vs IPTp SP): Low birth weight.
Time Frame: day 0, birth
day 0, birth
Trial 2 (CTX+IPTp MQ vs. CTX+IPTp placebo): Peripheral parasitaemia.
Time Frame: day 0, delivery
day 0, delivery

Secondary Outcome Measures

Outcome Measure
Time Frame
Trial 1: Prevalence of placental P. falciparum infection. Prevalence of moderate maternal anaemia at delivery.
Time Frame: day 0, delivery
day 0, delivery
Trial 2: Prevalence of placental P. falciparum infection. Prevalence of low birth weight babies (< 2500 g).
Time Frame: day 0, birth
day 0, birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Clinic of Barcelona

Collaborators

Centers for Disease Control and Prevention
Ifakara Health Institute
Kenya Medical Research Institute
Centro de Investigação em Saúde de Manhiça
Albert Schweitzer Hospital
Institut de Recherche pour le Developpement
Université d'Abomey-Calavi
Barcelona Centre for International Health Research
Institute of Tropical Medicine, University of Tuebingen
Vienna School of Clinical Research (VSCR), Austria.
Malaria in Pregnancy Consortium

Investigators

  • Principal Investigator: Clara Menendez, MD, PhD, Barcelona Centre for International Health Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (ACTUAL)

December 1, 2012

Study Completion (ACTUAL)

December 1, 2013

Study Registration Dates

First Submitted

December 18, 2008

First Submitted That Met QC Criteria

December 18, 2008

First Posted (ESTIMATE)

December 19, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

March 20, 2014

Last Update Submitted That Met QC Criteria

March 19, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IP.07.31080.002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Sulphadoxine-pyrimethamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malawi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe