Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy

HIV Infections Clinical Trial

— MiPPAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00811421
• Other study ID #: IP.07.31080.002
• Status: Completed
• Phase: N/A
• First received: December 18, 2008
• Last updated: March 19, 2014
• Start date: September 2009
• Est. completion date: December 2013

Study information

• Verified date: March 2014
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics CommitteeBenin: Ethics CommitteeGabon:Ethics CommitteeUnited States: Institutional Review BoardKenya: Ethical Review CommitteeTanzania: Ethics CommitteeMozambique: Ministry of Health (MISAU)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5820
• Est. completion date: December 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections
• Malaria
• Pregnancy

Intervention

Drug:
• Sulphadoxine-pyrimethamine
SP oral administration (500mg sulphadoxine and 25mg pyrimethamine) as IPTp at the 1st and 2nd Antenatal Clinic visit
• Mefloquine (full dose)
MQ oral administration (15 mg/Kg) on 1 day at the 1st and 2nd Antenatal Clinic visit as IPTp
• Mefloquine (split dose)
MQ oral administration (15 mg/kg) split dose over 2 days at the 1st and 2nd ANC visit as IPTp
• placebo
MQ-placebo oral administration at the 1st, 2nd and 3rd Antenatal Clinic visit as IPTp
• mefloquine
MQ oral administration (15 mg/Kg) at the 1st and 2nd Antenatal Clinic visit as IPTp

Locations

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

Sponsors (12)

Lead Sponsor

Collaborator

Hospital Clinic of Barcelona

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

Countries where clinical trial is conducted

Benin,  Gabon,  Kenya,  Mozambique,  Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trial 1 (IPTp MQ vs IPTp SP): Low birth weight.		day 0, birth	No
Primary	Trial 2 (CTX+IPTp MQ vs. CTX+IPTp placebo): Peripheral parasitaemia.		day 0, delivery	No
Secondary	Trial 1: Prevalence of placental P. falciparum infection. Prevalence of moderate maternal anaemia at delivery.		day 0, delivery	No
Secondary	Trial 2: Prevalence of placental P. falciparum infection. Prevalence of low birth weight babies (< 2500 g).		day 0, birth	No