Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria
Information source: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria in Pregnancy
Intervention: Dihydroartemisinin-piperaquine (Drug); Artesunate-mefloquine (Drug); Artesunate-amodiaquine (Drug); Artemether-lumefantrine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Institute of Tropical Medicine, Belgium Official(s) and/or principal investigator(s): Umberto D'Alessandro, MD, Study Chair, Affiliation: Institute Tropical Medicine Belgium and MRC Unit in The Gambia Tinto Halidou, PharmD, Principal Investigator, Affiliation: Centre Muraz
Summary
Malaria is the most important human parasitic disease and is responsible of high morbidity
and mortality in resource-poor countries. Pregnant women, who are a high-risk group, are
almost always excluded from clinical trials; thus, the investigators lack sufficient
information on the safety and efficacy of most antimalarials in pregnancy. The
recommendation of the World Health Organization to use artemisinin combination therapy (ACT)
in the 2nd and 3rd trimester is already implemented in several African countries, however
documentation of their efficacy and safety in pregnancy is still limited. Thus, the
investigators propose to evaluate the efficacy and safety of 4 ACT(artemether-lumefantrine,
amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), when used
to treat pregnant women with P. falciparum malaria; the results will help to recommend the
optimal therapy for this high-risk group in Africa.
Clinical Details
Official title: Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Treatment Failure (PCR adjusted)Safety profiles including significant changes in relevant laboratory values
Secondary outcome: Time to failurePCR unadjusted treatment failure Gametocyte carriage (gametocyte-weeks) Asexual parasite clearance time Gametocytaemia (prevalence and density) Haemoglobin changes The presence of acute, chronic or past infection of the placenta (prevalence) Mean birth weight and prevalence of low birth weight newborns In vitro vitro and search of molecular markers related to drug resistance Determination of the PK profile of MQ, AQ and PQ (on 120 women/treatment)
Detailed description:
Malaria is the most important human parasitic disease. Although pregnant women are a
high-risk group, they are almost systematically excluded from clinical trials, for fear of
teratogenicity and embryotoxicity; thus, we generally lack sufficient information on the
safety and efficacy of most antimalarials in pregnancy, as well as evidence-based
recommendations for the prevention and treatment of malaria during pregnancy.
The WHO recommendation to use artemisinin combination therapy (ACT) in the 2nd and 3rd
trimester is already implemented in several African countries. However, the documentation of
their efficacy and safety in pregnancy is still limited, especially concerning the African
contexts.
Therefore, we propose to test 4 fixed-dose combinations (artemether-lumefantrine,
amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), to
evaluate their efficacy and safety when administered to pregnant women (2nd and 3rd
trimester) infected with P. falciparum. Explanatory variables will be collected for
treatment failure (PCR-corrected) and for recurrent parasitaemia. The primary hypothesis
tested will be the clinical equivalence (pair-wise non-inferiority) of the 4 treatment
regimens with clinical equivalence defined as difference in treatment failure rates (PCR
corrected) of 5% or less.
In addition, an attempt will be done to carry out in vitro testing at the time of recurrent
infection. However, the success of the test will depend on the parasite density. In
addition, blood samples collected on filter paper at day 0 and at day of recurrent
parasitaemia will be genotyped for the search of known molecular markers related to drug
resistance. Not all samples will be analyzed; rather these will be selected according to the
therapeutic response so that the prevalence of molecular markers will be compared between
treatment successes, true treatment failures and new infections.
Eligibility
Minimum age: 15 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Gestation of at least 16 weeks and <37 weeks;
- P. falciparum monoinfection of any density, with or without symptoms
- Hb equal or higher than 7 g/dL;
- At least 15 years old;
- Residence within the health facility catchment's area;
- Willing to deliver at the health facility;
- Willing to adhere to study requirements (including in Zambia and Malawi, HIV VCT)
- Ability to provide written informed consent; if the woman is minor of age/not
emancipated, the consent must be given by a parent or legal guardian according to
national law (however, in this case, the investigator is responsible to check that
the woman herself is also freely willing to take part in the study, and the woman
will be asked to sign for "assent").
Exclusion Criteria:
- History of allergic reactions to the study drugs;
- History of known pregnancy complications or bad obstetric history such as repeated
stillbirths or eclampsia;
- History or presence of major illnesses likely to influence pregnancy outcome
including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
- Current cotrimoxazole prophylaxis or ARV treatment;
- Any significant illness at the time of screening that requires hospitalization,
including severe malaria;
- Intent to move out of the study catchment area before delivery or deliver at
relative's home out of the catchment area.
- Prior enrollment in the study or concurrent enrollment in another study.
- Unable to take oral medication
- Clear evidence of recent (1 week) treatment with antimalarials or antimicrobials with
antimalarial activity (clindamycin; azythromycin; etc.)
Locations and Contacts
ISSR/Centre Muraz, Nanoro, Burkina Faso
ISSR/Centre Muraz, Nazoanga, Burkina Faso
Effiduase Government Hospital, Effiduase, Ghana
Kwame Nkrumah University of Science & Technology, Kumasi, Ejisu Sekyere East, Ashanti Region, Ghana
Kwame Nrumah University of Science and Technology, Kumasi, Juaben Government Hospital, Ashanti Region, Ghana
College of Medicine, University of Malawi, Chikwawa District Hospital, Blantyre, Malawi
St Paul Hospital, Nchelenge, Nchelenge District, Zambia
Additional Information
Starting date: June 2010
Last updated: May 28, 2015
|