MiPPAD: Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy

Sponsor

Hospital Clinic of Barcelona (Other)

Overall Status

Completed

CT.gov ID

NCT00811421

Collaborator

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

5,820

Enrollment

Locations

Arms

Duration (Months)

1164

Patients Per Site

22.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Pregnancy Malaria HIV Infections	Drug: Sulphadoxine-pyrimethamine Drug: Mefloquine (full dose) Drug: Mefloquine (split dose) Drug: placebo Drug: mefloquine	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

5820 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Trial 1 (IPTp MQ vs IPTp SP): Low birth weight. [day 0, birth]
Trial 2 (CTX+IPTp MQ vs. CTX+IPTp placebo): Peripheral parasitaemia. [day 0, delivery]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country
1	Faculté des Sciences de la Santé (FSS), Université d'Abomey Calavi	Allada		Benin
2	Medical Rsearch Unit (MRU), Albert Schweitzer Hospital	Lambaréné		Gabon
3	Kenya Medical Research Institute (KEMRI)/ CDC	Kisumu		Kenya
4	Centro de Investigaçao em Saúde da Manhiça (CISM)	Manhiça	Maputo	Mozambique
5	Ifakara Health Institute (IHI)	Dodoma		Tanzania