Evaluation of Alternative Antimalarial Drugs for Malaria in Pregnancy

NCT00811421 | Completed DMC

• 1 other identifier: IP.07.31080.002
• Study Type: interventional
• Target: 5,820
• Locations: 5 countries
• Sites: 5

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.

Conditions

Pregnancy; Malaria; HIV Infections

Keywords

Malaria; Pregnancy; HIV; Prevention; Malaria prevention

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (5)

Trial 1: IPTp-SP+LLITNs

ACTIVE COMPARATOR

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

Trial 1: IPTp-MQ (full dose) + LLITNs

EXPERIMENTAL

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)

Trial 1: IPTp-MQ (split dose)+LLITNs

EXPERIMENTAL

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)

Trial 2: CTX+IPTp-Placebo+LLITNs

EXPERIMENTAL

HIV-positive pregnant women receiving 3 doses of IPTp (placebo) in the context of long lasting Insecticide Treated Nets (LLITNs)

Drug: placebo

Trial 2: CTX + IPTp-MQ+ LLITNs

EXPERIMENTAL

HIV-positive pregnant women receiving 3 doses of IPTp (15 mg/Kg) in the context of long lasting Insecticide Treated Nets (LLITNs)

Drug: mefloquine

Interventions

Sulphadoxine-pyrimethamine DRUG

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

Trial 1: IPTp-SP+LLITNs

Mefloquine (full dose) DRUG

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

Trial 1: IPTp-MQ (full dose) + LLITNs

Mefloquine (split dose) DRUG

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

Trial 1: IPTp-MQ (split dose)+LLITNs

placebo DRUG

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

Trial 2: CTX+IPTp-Placebo+LLITNs

mefloquine DRUG

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

Trial 2: CTX + IPTp-MQ+ LLITNs

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (5)

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

Allada, Benin

Location

Medical Rsearch Unit (MRU), Albert Schweitzer Hospital

Lambaréné, Gabon

Location

Kenya Medical Research Institute (KEMRI)/ CDC

Kisumu, Kenya

Location

Centro de Investigaçao em Saúde da Manhiça (CISM)

Manhiça, Maputo Province, Mozambique

Location

Ifakara Health Institute (IHI)

Dodoma, Tanzania

Location

Related Publications (16)

• 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.

  PMID: 39324693 DERIVED

• 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.

  PMID: 34297062 DERIVED

• 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.

  PMID: 33561169 DERIVED

• 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.

  PMID: 31318954 DERIVED

• 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.

  PMID: 29876999 DERIVED

• 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.

  PMID: 29683544 DERIVED

• 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.

  PMID: 28712360 DERIVED

• 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.

  PMID: 28575010 DERIVED

• 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.

  PMID: 27940685 DERIVED

• 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.

  PMID: 27357200 DERIVED

• 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.

  PMID: 26978384 DERIVED

• 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.

  PMID: 26905278 DERIVED

• 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.

  PMID: 26055847 DERIVED

• 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.

  PMID: 25915616 DERIVED

• 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.

  PMID: 25247995 DERIVED

• 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.

  PMID: 25247709 DERIVED

MeSH Terms

Conditions

Malaria; HIV Infections

Interventions

fanasil, pyrimethamine drug combination; Mefloquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clara Menendez, MD, PhD

  Barcelona Centre for International Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: September 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2013
• Last Updated: March 20, 2014

Record last verified: 2014-03

Locations

BE (1); KE (1); TA (1); GA (1); MO (1)