A Phase 3 interventional study of Dihydroartemisinin-piperaquine (DHA-PPQ) and Placebo Oral Tablet in Malaria, HIV/AIDS and Pregnancy Related, sponsored by Barcelona Institute for Global Health. Completed at 2 sites in 2 countries. Open to female participants, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-01.
Sponsored by Barcelona Institute for Global Health · Phase 3, Interventional, and Prevention
Trial to evaluate the safety and efficacy of DHA-PPQ for Intermittent Preventive Treatment (IPTp) in HIV-infected pregnant women receiving cotrimoxazole prophylaxis (CTXp) and antiretroviral (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.
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
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:
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).
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's enrollment of 666 is above the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →Barcelona Institute for Global Health is the lead sponsor of 24 studies on the registry; 5 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Monthly IPTp-DHA-PPQ over three days plus daily ARVs and cotrimoxazole prophylaxis
Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
Monthly IPTp-placebo over three days plus daily ARVs and cotrimoxazole prophylaxis
Drug: Placebo Oral Tablet
Drug pages: Artenimol · Piperaquine
Following physical examination, recruited women with more than 13 weeks of gestational age will receive IPTp-DHA-PPQ under supervision
Following physical examination, recruited women with more than 13 weeks of gestational age will receive IPTp-Placebo under supervision
Maternal parasitaemia at delivery
Presence of Plasmodium falciparum (P. falciparum) asexual parasites of any density in peripheral blood (determined by microscopy)
Time frame: Delivery
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
Composite malaria outcome: proportion of participants with malaria infection diagnosed
Any malaria confirmed infection during follow up, delivery and post-partum period (blood smear, malaria PCR, placental infection)
Time frame: From enrolment until one month after end of pregnancy (on average seven months of study follow up of women, depending on gestational age at inclusion)
Composite maternal malaria and anemia: proportion of particiapnts diganosed either with malaria or anemia
Time frame: At delivery
Composite adverse pregnancy outcome
LBW, miscarriage, stillbirth, prematurity
Time frame: Birth
Plan to share: Yes — 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 information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Project metadata will be made available in formal reports to key stakeholders as soon as possible and to the wider public within 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
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Artenimol · Piperaquine
Barcelona Institute for Global Health