Efficacy of Antifolates Against Malaria in HIV-infected Pregnant Women and the Emergence of Induced Resistance in Plasmodium Falciparum

NCT01746199 | Completed Phase 3 DMC

• 1 other identifier: 2012-03
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 4

Brief Summary

Given the resistance emergence of malaria in pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) and the burden of this infection among pregnant women infected by HIV it is urgent to seek a more effective alternative treatment to optimize the prevention of malaria. Cotrimoxazole (CTM), actually administered daily as a prophylactic mean to opportunistic infections for HIV infected patients, showed encouraging results in preventing malaria in pregnant women. However, these results must be confirmed by randomized trials, particularly in pregnant women. The main objective of this clinical trial is to compare the efficacy of cotrimoxazole (CTM), administered once daily with IPT-SP (3 curative doses spaced one month) on placental parasitaemia in pregnant women infected with HIV and cluster of differentiation 4 (CD4) \> 350 cells/mm3. The main hypothesis is based on the premise that cotrimoxazole is more effective than IPT-SP for placental parasitaemia. This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses. If this hypothesis is proven, cotrimoxazole could be recommended as prophylaxis for HIV-positive pregnant women, whatever their CD4+ cell count. In this study, the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV-positive pregnant women express more dhfr and dhps resistance markers.

Conditions

Malaria in Pregnancy; HIV Infection

Outcome Measures

Primary Outcomes (1)

• placental parasitaemia

  microscopic observation and confirmation by Polymerase Chain Reaction (PCR)

  at parturition

Secondary Outcomes (3)

• observance CTM prophylaxis

  until the end of pregnancy

• occurrence of specific events related to the effectiveness of CTM prophylaxis and IPT-SP

  until the end of pregnancy

• occurence of adverse events

  until the end of pregnancy

Study Arms (2)

cotrimoxazole daily prophylaxis

EXPERIMENTAL

cotrimoxazole daily prophylaxis

Drug: cotrimoxazole daily prophylaxis

Intermittent Preventive sulphadoxine-pyrimethamine Treatment

ACTIVE COMPARATOR

Referent treatment given according WHO recommendations

Drug: sulphadoxine-pyrimethamine

Interventions

cotrimoxazole daily prophylaxis DRUG

Also known as: - CTM, - Sulfamethoxazole- trimethoprime, - Bactrim®

cotrimoxazole daily prophylaxis

sulphadoxine-pyrimethamine DRUG

Intermittent preventive sulphadoxine-pyrimethamine treatment

Also known as: - SP, - sulfadoxine-pyrimethamine, - Fansidar®

Intermittent Preventive sulphadoxine-pyrimethamine Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥ 18 years
• HIV positivity
• gestational age between 16 and 28 weeks
• CD4+ count \> 350 cells/mm3 and no sign of WHO stage 2, 3 or 4;
• agreement to attend all the antenatal consultations for the study
• willingness to adhere to all requirements of the study (including HIV-1 voluntary counseling and testing)
• signed informed consent

You may not qualify if:

• psychological instability that could interfere with compliance;
• hypersensitivity to sulfamides or dermatological disease(eczema, pemphigoid exanthema) that would increase the risk for severe reactions to the drugs being tested
• severe anaemia (Hb\<7 g/dl)and any other severe disease
• known hepatic cardiac or renal disease

Sponsors & Collaborators

• Institut Pasteur: lead
• Institut Pasteur de Bangui: collaborator

Study Sites (4)

Maternité de l'Hôpital communautaire

Bangui, Central African Republic

Location

Maternité de l'Hôpital de l'Amitié

Bangui, Central African Republic

Location

Maternité de la Gendarmerie Nationale

Bangui, Central African Republic

Location

Maternité du centre de santé des Castors

Bangui, Central African Republic

Location

Related Publications (2)

• 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

• Manirakiza A, Sepou A, Serdouma E, Gondje S, Bata GG, Moussa S, Boulay A, Moyen JM, Sakanga O, Le-Fouler L, Kazanji M, Vray M. Effectiveness of two antifolate prophylactic strategies against malaria in HIV-positive pregnant women in Bangui, Central African Republic: study protocol for a randomized controlled trial (MACOMBA). Trials. 2013 Aug 14;14:255. doi: 10.1186/1745-6215-14-255.

  PMID: 23945130 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; 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)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Muriel Vray

  Unité d'épidémiologie des maladies émergentes, Institut Pasteur Paris, France

  STUDY DIRECTOR

• Alexandre Manirakiza, MD

  Unité d'Epidémiologie, Institut Pasteur de Bangui, Central African Republic

  PRINCIPAL INVESTIGATOR

• Mirdad Kazanji

  Director of the Institut Pasteur de Bangui, Central African Republic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2012
• First Posted: December 10, 2012
• Study Start: December 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2019
• Last Updated: November 30, 2020

Record last verified: 2020-11

Locations

CE (4)