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

This study has been completed.
Sponsor:
Collaborators:
Barcelona Centre for International Health Research
Institute of Tropical Medicine, University of Tuebingen
Institut de Recherche pour le Developpement
Université d'Abomey-Calavi
Albert Schweitzer Hospital
Kenya Medical Research Institute
Ifakara Health Institute
Centro de Investigacao em Saude de Manhica
Vienna School of Clinical Research (VSCR), Austria.
Malaria in Pregnancy (MiP) Consortium
Information provided by:
Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00811421
First received: December 18, 2008
Last updated: March 19, 2014
Last verified: March 2014

December 18, 2008
March 19, 2014
September 2009
December 2012   (final data collection date for primary outcome measure)
  • Trial 1 (IPTp MQ vs IPTp SP): Low birth weight. [ Time Frame: day 0, birth ] [ Designated as safety issue: No ]
  • Trial 2 (CTX+IPTp MQ vs. CTX+IPTp placebo): Peripheral parasitaemia. [ Time Frame: day 0, delivery ] [ Designated as safety issue: No ]
Trial 1 (IPTp MQ vs IPTp SP): Low birth weight. Trial 2 (CTX+IPTp MQ vs CTX+IPTp placebo): Peripheral parasitaemia [ Time Frame: Delivery ( depending on gestational age at recruitment) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00811421 on ClinicalTrials.gov Archive Site
  • Trial 1: Prevalence of placental P. falciparum infection. Prevalence of moderate maternal anaemia at delivery. [ Time Frame: day 0, delivery ] [ Designated as safety issue: No ]
  • Trial 2: Prevalence of placental P. falciparum infection. Prevalence of low birth weight babies (< 2500 g). [ Time Frame: day 0, birth ] [ Designated as safety issue: No ]
Trial 1:Prevalence of placental P. falciparum infection.Prevalence of moderate maternal anaemia at delivery. Trial 2:Prevalence of placental P. falciparum infection.Prevalence of low birth weight babies (<2500 g) [ Time Frame: Delivery (depending on gestational age at recruitment) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Pregnancy
  • Malaria
  • HIV Infections
  • Drug: Sulphadoxine-pyrimethamine
    SP oral administration (500mg sulphadoxine and 25mg pyrimethamine) as IPTp at the 1st and 2nd Antenatal Clinic visit
  • Drug: Mefloquine (full dose)
    MQ oral administration (15 mg/Kg) on 1 day at the 1st and 2nd Antenatal Clinic visit as IPTp
  • Drug: Mefloquine (split dose)
    MQ oral administration (15 mg/kg) split dose over 2 days at the 1st and 2nd ANC visit as IPTp
  • Drug: placebo
    MQ-placebo oral administration at the 1st, 2nd and 3rd Antenatal Clinic visit as IPTp
  • Drug: mefloquine
    MQ oral administration (15 mg/Kg) at the 1st and 2nd Antenatal Clinic visit as IPTp
  • 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)
    Intervention: Drug: Sulphadoxine-pyrimethamine
  • 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)
    Intervention: Drug: Mefloquine (full dose)
  • 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
    Intervention: Drug: Mefloquine (split dose)
  • 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)
    Intervention: Drug: placebo
  • 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)
    Intervention: Drug: mefloquine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5820
December 2013
December 2012   (final data collection date for primary outcome measure)

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
Female
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
Benin,   Gabon,   Kenya,   Mozambique,   Tanzania
 
NCT00811421
IP.07.31080.002
Yes
Professor Clara Menendez Santos, Barcelona Centre for International Health Research (CRESIB), Spain
Hospital Clinic of Barcelona
  • Barcelona Centre for International Health Research
  • Institute of Tropical Medicine, University of Tuebingen
  • Institut de Recherche pour le Developpement
  • Université d'Abomey-Calavi
  • Albert Schweitzer Hospital
  • Kenya Medical Research Institute
  • Ifakara Health Institute
  • Centro de Investigacao em Saude de Manhica
  • Vienna School of Clinical Research (VSCR), Austria.
  • Centers for Disease Control and Prevention
  • Malaria in Pregnancy (MiP) Consortium
Principal Investigator: Clara Menendez, MD, PhD Barcelona Centre for International Health Research
Hospital Clinic of Barcelona
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP