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
  Purpose

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.


Condition Intervention
Pregnancy
Malaria
HIV Infections
Drug: Sulphadoxine-pyrimethamine
Drug: Mefloquine (full dose)
Drug: Mefloquine (split dose)
Drug: placebo
Drug: mefloquine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Evaluation of the Safety and Efficacy of Mefloquine as Intermittent Preventive Treatment of Malaria in Pregnancy

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 5820
Study Start Date: September 2009
Study Completion Date: December 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811421

Locations
Benin
Faculté des Sciences de la Santé (FSS), Université d'Abomey Calavi
Allada, Benin
Gabon
Medical Rsearch Unit (MRU), Albert Schweitzer Hospital
Lambaréné, Gabon
Kenya
Kenya Medical Research Institute (KEMRI)/ CDC
Kisumu, Kenya
Mozambique
Centro de Investigaçao em Saúde da Manhiça (CISM)
Manhiça, Maputo, Mozambique
Tanzania
Ifakara Health Institute (IHI)
Dodoma, Tanzania
Sponsors and Collaborators
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.
Malaria in Pregnancy (MiP) Consortium
Investigators
Principal Investigator: Clara Menendez, MD, PhD Barcelona Centre for International Health Research
  More Information

No publications provided

Responsible Party: Professor Clara Menendez Santos, Barcelona Centre for International Health Research (CRESIB), Spain
ClinicalTrials.gov Identifier: NCT00811421     History of Changes
Other Study ID Numbers: IP.07.31080.002
Study First Received: December 18, 2008
Last Updated: March 19, 2014
Health Authority: Spain: Ethics Committee
Benin: Ethics Committee
Gabon:Ethics Committee
United States: Institutional Review Board
Kenya: Ethical Review Committee
Tanzania: Ethics Committee
Mozambique: Ministry of Health (MISAU)

Keywords provided by Hospital Clinic of Barcelona:
Malaria
Pregnancy
HIV
Prevention
Malaria prevention

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Antimalarials
Mefloquine
Pyrimethamine
Sulfadoxine
Fanasil, pyrimethamine drug combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on September 15, 2014