Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy

NCT ID: NCT00811421

Last Updated: 2014-03-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

5820 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2013-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pregnancy Malaria HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Sulphadoxine-pyrimethamine

Intervention Type DRUG

SP oral administration (500mg sulphadoxine and 25mg pyrimethamine) as IPTp at the 1st and 2nd Antenatal Clinic visit

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)

Group Type EXPERIMENTAL

Mefloquine (full dose)

Intervention Type DRUG

MQ oral administration (15 mg/Kg) on 1 day at the 1st and 2nd Antenatal Clinic visit as IPTp

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

Group Type EXPERIMENTAL

Mefloquine (split dose)

Intervention Type DRUG

MQ oral administration (15 mg/kg) split dose over 2 days at the 1st and 2nd ANC visit as IPTp

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)

Group Type EXPERIMENTAL

placebo

Intervention Type DRUG

MQ-placebo oral administration at the 1st, 2nd and 3rd Antenatal Clinic visit as IPTp

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)

Group Type EXPERIMENTAL

mefloquine

Intervention Type DRUG

MQ oral administration (15 mg/Kg) at the 1st and 2nd Antenatal Clinic visit as IPTp

Interventions

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Sulphadoxine-pyrimethamine

SP oral administration (500mg sulphadoxine and 25mg pyrimethamine) as IPTp at the 1st and 2nd Antenatal Clinic visit

Intervention Type DRUG

Mefloquine (full dose)

MQ oral administration (15 mg/Kg) on 1 day at the 1st and 2nd Antenatal Clinic visit as IPTp

Intervention Type DRUG

Mefloquine (split dose)

MQ oral administration (15 mg/kg) split dose over 2 days at the 1st and 2nd ANC visit as IPTp

Intervention Type DRUG

placebo

MQ-placebo oral administration at the 1st, 2nd and 3rd Antenatal Clinic visit as IPTp

Intervention Type DRUG

mefloquine

MQ oral administration (15 mg/Kg) at the 1st and 2nd Antenatal Clinic visit as IPTp

Intervention Type DRUG

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Barcelona Centre for International Health Research

OTHER

Sponsor Role collaborator

Institute of Tropical Medicine, University of Tuebingen

OTHER

Sponsor Role collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role collaborator

Université d'Abomey-Calavi

OTHER

Sponsor Role collaborator

Albert Schweitzer Hospital

OTHER

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

Ifakara Health Institute

OTHER

Sponsor Role collaborator

Centro de Investigacao em Saude de Manhica

OTHER

Sponsor Role collaborator

Vienna School of Clinical Research (VSCR), Austria.

UNKNOWN

Sponsor Role collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

Malaria in Pregnancy Consortium

OTHER

Sponsor Role collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role lead

Responsible Party

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Barcelona Centre for International Health Research (CRESIB), Spain

Principal Investigators

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Clara Menendez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Barcelona Centre for International Health Research

Locations

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Faculté des Sciences de la Santé (FSS), Université d'Abomey Calavi

Allada, , Benin

Site Status

Medical Rsearch Unit (MRU), Albert Schweitzer Hospital

Lambaréné, , Gabon

Site Status

Kenya Medical Research Institute (KEMRI)/ CDC

Kisumu, , Kenya

Site Status

Centro de Investigaçao em Saúde da Manhiça (CISM)

Manhiça, Maputo Province, Mozambique

Site Status

Ifakara Health Institute (IHI)

Dodoma, , Tanzania

Site Status

Countries

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Benin Gabon Kenya Mozambique Tanzania

References

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Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.

Reference Type DERIVED
PMID: 39324693 (View on PubMed)

Garrison A, Boivin MJ, Fievet N, Zoumenou R, Alao JM, Massougbodji A, Cot M, Bodeau-Livinec F. The Effects of Malaria in Pregnancy on Neurocognitive Development in Children at 1 and 6 Years of Age in Benin: A Prospective Mother-Child Cohort. Clin Infect Dis. 2022 Mar 9;74(5):766-775. doi: 10.1093/cid/ciab569.

Reference Type DERIVED
PMID: 34297062 (View on PubMed)

Zoleko-Manego R, Mischlinger J, Dejon-Agobe JC, Basra A, Mackanga JR, Akerey Diop D, Adegnika AA, Agnandji ST, Lell B, Kremsner PG, Matsiegui PB, Gonzalez R, Menendez C, Ramharter M, Mombo-Ngoma G. Birth weight, growth, nutritional status and mortality of infants from Lambarene and Fougamou in Gabon in their first year of life. PLoS One. 2021 Feb 9;16(2):e0246694. doi: 10.1371/journal.pone.0246694. eCollection 2021.

Reference Type DERIVED
PMID: 33561169 (View on PubMed)

Garrison A, Khoshnood B, Courtin D, Milet J, Garcia A, Massougbodji A, Ayotte P, Cot M, Bodeau-Livinec F. Blood lead level in infants and subsequent risk of malaria: A prospective cohort study in Benin, Sub-Saharan Africa. PLoS One. 2019 Jul 18;14(7):e0220023. doi: 10.1371/journal.pone.0220023. eCollection 2019.

Reference Type DERIVED
PMID: 31318954 (View on PubMed)

Mireku MO, Davidson LL, Zoumenou R, Massougbodji A, Cot M, Bodeau-Livinec F. Consequences of prenatal geophagy for maternal prenatal health, risk of childhood geophagy and child psychomotor development. Trop Med Int Health. 2018 Aug;23(8):841-849. doi: 10.1111/tmi.13088. Epub 2018 Jun 22.

Reference Type DERIVED
PMID: 29876999 (View on PubMed)

Moya-Alvarez V, Ouedraogo S, Accrombessi M, Cot M. High folate levels are not associated with increased malaria risk but with reduced anaemia rates in the context of high-dosed folate supplements and intermittent preventive treatment against malaria in pregnancy with sulphadoxine-pyrimethamine in Benin. Trop Med Int Health. 2018 Jun;23(6):582-588. doi: 10.1111/tmi.13064. Epub 2018 May 21.

Reference Type DERIVED
PMID: 29683544 (View on PubMed)

Ndam NT, Mbuba E, Gonzalez R, Cistero P, Kariuki S, Sevene E, Ruperez M, Fonseca AM, Vala A, Maculuve S, Jimenez A, Quinto L, Ouma P, Ramharter M, Aponte JJ, Nhacolo A, Massougbodji A, Briand V, Kremsner PG, Mombo-Ngoma G, Desai M, Macete E, Cot M, Menendez C, Mayor A. Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities. BMC Med. 2017 Jul 17;15(1):130. doi: 10.1186/s12916-017-0893-6.

Reference Type DERIVED
PMID: 28712360 (View on PubMed)

Gonzalez R, Ruperez M, Sevene E, Vala A, Maculuve S, Bulo H, Nhacolo A, Mayor A, Aponte JJ, Macete E, Menendez C. Effects of HIV infection on maternal and neonatal health in southern Mozambique: A prospective cohort study after a decade of antiretroviral drugs roll out. PLoS One. 2017 Jun 2;12(6):e0178134. doi: 10.1371/journal.pone.0178134. eCollection 2017.

Reference Type DERIVED
PMID: 28575010 (View on PubMed)

Mireku MO, Davidson LL, Boivin MJ, Zoumenou R, Massougbodji A, Cot M, Bodeau-Livinec F. Prenatal Iron Deficiency, Neonatal Ferritin, and Infant Cognitive Function. Pediatrics. 2016 Dec;138(6):e20161319. doi: 10.1542/peds.2016-1319. Epub 2016 Nov 17.

Reference Type DERIVED
PMID: 27940685 (View on PubMed)

Mombo-Ngoma G, Mackanga JR, Gonzalez R, Ouedraogo S, Kakolwa MA, Manego RZ, Basra A, Ruperez M, Cot M, Kabanywany AM, Matsiegui PB, Agnandji ST, Vala A, Massougbodji A, Abdulla S, Adegnika AA, Sevene E, Macete E, Yazdanbakhsh M, Kremsner PG, Aponte JJ, Menendez C, Ramharter M. Young adolescent girls are at high risk for adverse pregnancy outcomes in sub-Saharan Africa: an observational multicountry study. BMJ Open. 2016 Jun 29;6(6):e011783. doi: 10.1136/bmjopen-2016-011783.

Reference Type DERIVED
PMID: 27357200 (View on PubMed)

Bodeau-Livinec F, Glorennec P, Cot M, Dumas P, Durand S, Massougbodji A, Ayotte P, Le Bot B. Elevated Blood Lead Levels in Infants and Mothers in Benin and Potential Sources of Exposure. Int J Environ Res Public Health. 2016 Mar 11;13(3):316. doi: 10.3390/ijerph13030316.

Reference Type DERIVED
PMID: 26978384 (View on PubMed)

Ruperez M, Gonzalez R, Mombo-Ngoma G, Kabanywanyi AM, Sevene E, Ouedraogo S, Kakolwa MA, Vala A, Accrombessi M, Briand V, Aponte JJ, Manego Zoleko R, Adegnika AA, Cot M, Kremsner PG, Massougbodji A, Abdulla S, Ramharter M, Macete E, Menendez C. Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study. PLoS Med. 2016 Feb 23;13(2):e1001964. doi: 10.1371/journal.pmed.1001964. eCollection 2016 Feb.

Reference Type DERIVED
PMID: 26905278 (View on PubMed)

Mireku MO, Davidson LL, Koura GK, Ouedraogo S, Boivin MJ, Xiong X, Accrombessi MM, Massougbodji A, Cot M, Bodeau-Livinec F. Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children. Pediatrics. 2015 Jul;136(1):e76-83. doi: 10.1542/peds.2015-0491. Epub 2015 Jun 8.

Reference Type DERIVED
PMID: 26055847 (View on PubMed)

Sicuri E, Fernandes S, Macete E, Gonzalez R, Mombo-Ngoma G, Massougbodgi A, Abdulla S, Kuwawenaruwa A, Katana A, Desai M, Cot M, Ramharter M, Kremsner P, Slustker L, Aponte J, Hanson K, Menendez C. Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy. PLoS One. 2015 Apr 27;10(4):e0125072. doi: 10.1371/journal.pone.0125072. eCollection 2015.

Reference Type DERIVED
PMID: 25915616 (View on PubMed)

Gonzalez R, Desai M, Macete E, Ouma P, Kakolwa MA, Abdulla S, Aponte JJ, Bulo H, Kabanywanyi AM, Katana A, Maculuve S, Mayor A, Nhacolo A, Otieno K, Pahlavan G, Ruperez M, Sevene E, Slutsker L, Vala A, Williamsom J, Menendez C. Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial. PLoS Med. 2014 Sep 23;11(9):e1001735. doi: 10.1371/journal.pmed.1001735. eCollection 2014 Sep.

Reference Type DERIVED
PMID: 25247995 (View on PubMed)

Gonzalez R, Mombo-Ngoma G, Ouedraogo S, Kakolwa MA, Abdulla S, Accrombessi M, Aponte JJ, Akerey-Diop D, Basra A, Briand V, Capan M, Cot M, Kabanywanyi AM, Kleine C, Kremsner PG, Macete E, Mackanga JR, Massougbodgi A, Mayor A, Nhacolo A, Pahlavan G, Ramharter M, Ruperez M, Sevene E, Vala A, Zoleko-Manego R, Menendez C. Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial. PLoS Med. 2014 Sep 23;11(9):e1001733. doi: 10.1371/journal.pmed.1001733. eCollection 2014 Sep.

Reference Type DERIVED
PMID: 25247709 (View on PubMed)

Other Identifiers

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IP.07.31080.002

Identifier Type: -

Identifier Source: org_study_id

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