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Improving Maternal heAlth by Reducing Malaria in African HIV Women (MAMAH)

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ClinicalTrials.gov Identifier: NCT03671109
Recruitment Status : Not yet recruiting
First Posted : September 14, 2018
Last Update Posted : August 8, 2019
Sponsor:
Collaborators:
Medicines for Malaria Venture
Universität Tübingen
Centre de Recherche Médicale de Lambaréné
Medical University of Vienna
Bernhard Nocht Institute for Tropical Medicine
Centro de Investigação em Saúde de Manhiça
Information provided by (Responsible Party):
Barcelona Institute for Global Health

Tracking Information
First Submitted Date  ICMJE September 6, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date August 8, 2019
Estimated Study Start Date  ICMJE September 2019
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
Maternal parasitaemia at delivery [ Time Frame: Delivery ]
Presence of Plasmodium falciparum (P. falciparum) asexual parasites of any density in peripheral blood (determined by microscopy)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03671109 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
  • Incidence of clinical malaria [ Time Frame: On average six months follow up during pregnancy ]
  • Incidence of all-cause admissions [ Time Frame: On average six months follow up during pregnancy ]
  • Incidence of all-cause outpatient attendances [ Time Frame: On average six months follow up during pregnancy ]
  • Frequency and severity of adverse events [ Time Frame: On average six months follow up during pregnancy ]
  • Mean haemoglobin concentration [ Time Frame: At delivery ]
  • Prevalence of submicroscopic P. falciparum peripheral parasitaemia [ Time Frame: At delivery ]
  • Prevalence of anaemia (Hb<11 g/dL) [ Time Frame: At delivery ]
  • Prevalence of severe anaemia (Hb<7 g/dL) [ Time Frame: At delivery ]
  • Mean CD4+ T cell counts levels [ Time Frame: At delivery ]
  • Proportion of women with detectable HIV viral load [ Time Frame: At delivery ]
  • Prevalence of placental P. falciparum infection [ Time Frame: At delivery ]
  • Prevalence of P. falciparum peripheral parasitaemia at the post-partum visit [ Time Frame: On average 42 days after end of pregnancy (post-partum visit) ]
  • Maternal mortality rate [ Time Frame: On average six months follow up during pregnancy and 42 days after end of pregnancy (post-partum visit) ]
  • Prevalence of P. falciparum parasitaemia in cord blood [ Time Frame: At birth ]
  • Prevalence of neonatal anaemia [ Time Frame: Neonatal period ( in first 28 days of life) ]
  • Mean birth weight [ Time Frame: At birth ]
  • Prevalence of low birth weight (<2500 g) [ Time Frame: At birth ]
  • Mean gestational age at birth [ Time Frame: At birth ]
  • Prevalence of prematurity [ Time Frame: At birth ]
  • Prevalence of embryo and foetal losses [ Time Frame: On average six months follow up during pregnancy ]
  • Prevalence of small for gestational age [ Time Frame: At birth ]
  • Frequency of congenital malformations [ Time Frame: At birth ]
  • Incidence of clinical malaria [ Time Frame: During first year of life ]
  • Neonatal mortality rate [ Time Frame: During neonatal period (during first 28 days of life) ]
  • Frequency of mother to child transmission of HIV at one and at 12 months of age [ Time Frame: During first year of life ]
  • Infant mortality rate [ Time Frame: During first year of life ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Improving Maternal heAlth by Reducing Malaria in African HIV Women
Official Title  ICMJE Evaluation of the Safety and Efficacy of Dihydroartemisinin-piperaquine for Intermittent Preventive Treatment of Malaria in HIV-infected Pregnant Women
Brief Summary Trial to evaluate the safety and efficacy of DHA-PPQ for Intermittent Preventive Treatment (IPTp) in HIV-infected pregnant women receiving cotrimoxazole prophylacis (CTXp) and antieretoviral (ARV) drugs and using long lasting insecticide treated nets will be conducted in Mozambique and Gabon where malaria and HIV infection are moderate to highly prevalent. In addition, the possibility for a PK interaction between DHA-PPQ and ARV drugs will be assessed in a sub-sample of participants. Women will receive ARV therapy according to national guidelines and their infants will be followed until one year of age to evaluate the impact of DHA-PPQ on MTCT-HIV.
Detailed Description

Background

Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. A recent trial showed that an effective antimalarial added to CTXp and long-lasting insecticide treated nets (LLITNs) in HIV-infected pregnant women improves malaria prevention and maternal health. However, the antimalarial used -mefloquine- was not well tolerated and it was associated with an increase in HIV viral load at delivery and a two-fold increased risk of MTCT-HIV. These findings highlight the need to find alternative drugs with better tolerability and safety profile to prevent malaria in this vulnerable group and to further study the pharmacological interactions between antimalarials and antiretrovirals (ARVs).

Dihydroartemisinin-piperaquine (DHA-PPQ), because of its long half-life and good tolerability has been shown to improve antimalarial protection in HIV-uninfected pregnant women, constituting the most promising candidate for IPTp in HIV-infected pregnant women. However, there is limited information on the pharmacokinetics of DHA-PPQ with concomitant use of ARV drugs and CTX, particularly in pregnant women.

Objectives

  1. To evaluate the safety, tolerability and efficacy of DHA-PPQ as IPTp for malaria prevention in HIV-infected pregnant women receiving daily CTXp and ARV drugs
  2. To assess the effect of DHA-PPQ as IPTp on mother to child transmission of HIV
  3. To study the effects of DHA-PPQ on the pharmacokinetics of clinically relevant doses of ARV drugs used for prevention of MTCT and treatment of HIV infection
  4. To evaluate the effectiveness of CTXp in clearing malaria parasites in HIV-infected pregnant women

Methods

The trial has been designed as a randomized double blind placebo-controlled superiority trial to evaluate the safety and efficacy of DHA-PPQ as IPTp in HIV-infected pregnant women taking daily CTXp and ARV drugs. The trial sites are located in Central and South Eastern sub-Saharan Africa (Gabon and Mozambique), where HIV prevalence among pregnant women ranges from 6 to 29%.

Based on previous estimations at the study sites and assuming a prevalence of peripheral parasitaemia at delivery of 7.5% with CTXp, it is estimated that 298 women per arm will be required to detect with 80% power a significant (p<0.05) decrease of 5% or more in the prevalence of peripheral parasitaemia in the CTXp+IPTp-DHA-PPQ group. In order to allow for 10% losses to follow up, it is calculated that 332 women/study arm will need to be recruited (total n=664). Furthermore, assuming a 5% MTCT-HIV in the control group, this sample size will have an 80% power to detect at the 5% level of significance, 2.2 times difference in the risk of MTCT-HIV.

The trial will have two study arms; HIV-infected pregnant women participating in the trial will be randomized to receive either:

  1. Monthly doses of IPTp-DHA-PPQ over three days plus daily ARVs and cotrimoxazole prophylaxis
  2. Monthly doses of IPTp-placebo over three days plus daily ARVs and cotrimoxazole prophylaxis

Women will receive ARV therapy according to national guidelines and their infants will be followed until one year of age to evaluate the impact of DHA-PPQ on MTCT-HIV.

Participants will be asked to visit the ANC monthly and to deliver at the study health facilities. Adherence to CTX prophylaxis and ARV therapy, as well as use of the LLITNs use will be assessed monthly at the scheduled antenatal care (ANC) clinic visits.

Pharmacokinetic (PK) sub-study The possibility for a PK interaction between DHA-PPQ and ARV drugs will be assessed in a sub-sample of participants (n=200).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Superiority clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind placebo-controlled
Primary Purpose: Prevention
Condition  ICMJE
  • Malaria
  • HIV/AIDS
  • Pregnancy Related
Intervention  ICMJE
  • Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
    Following physical examination, recruited women with more than 13 weeks of gestational age will receive IPTp-DHA-PPQ under supervision
  • Drug: Placebo Oral Tablet
    Following physical examination, recruited women with more than 13 weeks of gestational age will receive IPTp-Placebo under supervision
Study Arms  ICMJE
  • Experimental: IPTp-DHA-PPQ
    Monthly IPTp-DHA-PPQ over three days plus daily ARVs and cotrimoxazole prophylaxis
    Intervention: Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
  • Placebo Comparator: IPTp-Placebo
    Monthly IPTp-placebo over three days plus daily ARVs and cotrimoxazole prophylaxis
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2018)
644
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Permanent resident in the study area
  • Gestational age at the first antenatal visit ≤ 28 weeks
  • HIV seropositive status
  • Agreement to deliver in the study site's maternity(ies) wards

Exclusion Criteria:

  • Residence outside the study area or planning to move out in the following 10 months from enrolment
  • Gestational age at the first antenatal visit > 28 weeks of pregnancy
  • Known history of allergy to CTX
  • Known history of allergy or contraindications to DHA-PPQ
  • Participating in other intervention studies
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Raquel Gonzalez, MD, PhD +34932275400 ext 4144 raquel.gonzalez@isglobal.org
Contact: Mireia Piqueras, PhD +34932275400 ext 4141 mireia.piqueras@isglobal.org
Listed Location Countries  ICMJE Gabon,   Mozambique
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03671109
Other Study ID Numbers  ICMJE EDCTP- RIA2016MC-1613
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

The main findings of the clinical trial will be submitted for publication in a peer reviewed journal within 12 months of study completion through an open access mechanism, or otherwise made available publicly in compliance with H2020 open access requirements.

Primary project raw data will be published in the project website. This approach is taken to protect in particular the interests of the endemic country researchers and institutions and in acknowledgment of the primary research oversight by endemic country ethics review boards. At no stage will data containing personal information of research participants be released.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Project metadata will be made available in formal reports to key stakeholders as soon as possible and to the wider publicwithin 12 months after the end of the project. The announcement of the availability of the project metadata will be posted in the project website.
Access Criteria: Open Access
Responsible Party Barcelona Institute for Global Health
Study Sponsor  ICMJE Barcelona Institute for Global Health
Collaborators  ICMJE
  • Medicines for Malaria Venture
  • Universität Tübingen
  • Centre de Recherche Médicale de Lambaréné
  • Medical University of Vienna
  • Bernhard Nocht Institute for Tropical Medicine
  • Centro de Investigação em Saúde de Manhiça
Investigators  ICMJE
Study Director: Clara Menendez, MD, PhD Barcelona Institute for Global Health
PRS Account Barcelona Institute for Global Health
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP