Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Malaria in Pregnancy (ALN5P)
March 24, 2014 updated by: University of Oxford
Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Pregnant Women in the Democratic Republic of Congo
Malaria in pregnancy is a major cause of maternal and newborn morbidity and mortality in sub-Saharan Africa].
Effective antimalarial preventive and treatment regimens can significantly reduce malaria-related morbidity and mortality in the mother and baby.
However, therapeutic choices are limited by concerns about possible toxicity to the fetus and because of these concerns pregnant women are normally excluded from clinical trials.
This, combined with the lack of adverse events reporting system, results in a scarcity of data on drug safety and efficacy in pregnancy.
Moreover, changes in the maternal physiology in pregnancy often alter the pharmacokinetic of drugs.
Artemether-lumefantrine (ALN) is a highly efficacious artemisinin-based combination therapy approved by the World Health Organisation for use in the 2nd and 3rd trimesters, although it is still infrequently used in pregnancy and there is uncertainty as to the optimum dose.
The pharmacokinetics of ALN are altered in pregnancy, resulting in reduced plasma concentrations and while the standard adult dose is still effective in high transmission settings, where pregnant women have higher levels of immunity, efficacy is reduced significantly in low transmission settings where women have lower levels of immunity.
Inadequate antimalarial treatment dosing in pregnancy risks treatment failure or breakthrough infection and exposure of malaria parasites to sub-therapeutic drug concentrations thus selecting for drug resistance.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The aim of the current trial is to compare the standard 3-day regimen of artemether-lumefantrine to a 5-day regimen of artemether-lumefantrine in a group of pregnant women and a control of non-pregnant women with uncomplicated P. falciparum malaria.
The pharmacokinetics of lumefantrine is modified in pregnancy and the standard regimen used for treatment of adults might not be sufficient to cure malaria, therefore exposing pregnant women to sub-therapeutic drug levels and increased risk of clinical failure.
Previous pharmacokinetic studies have shown that the standard 3-day treatment during pregnancy results in reduced plasma concentrations of artemether, dihydroartemisinin and lumefantrine and a faster elimination of lumefantrine.
Low lumefantrine plasma concentrations at day 7 are associated with therapeutic failure.
Population-based simulations suggest that increased dose and treatment duration are needed for adequate drug exposure in these patients.
We propose to assess the pharmacokinetics of a longer regimen of artemether-lumefantrine, (10 doses of artemether-lumefantrine over five days) compared to the standard regimen, (6 doses of artemether-lumefantrine over three days) in a small group of pregnant African women with uncomplicated P. falciparum malaria.
The longer regimen should ensure that curative plasma concentration of lumefantrine is reached, and is unlikely to result in any increased frequency of adverse events.
Study Type
Interventional
Enrollment (Actual)
96
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Kinshasa, Congo
- University of Kinshasa, Democratic Republic of Congo
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion criteria for non pregnant women:
- Age ≥18 and ≤ 45 years
- P. falciparum parasitemia ≥ 100 parasites/μL and less than 200.000 parasites/μL
- Hematocrit ≥21%
- Negative HIV test
- Negative pregnancy test*
- Written informed consent provided
- Willing to stay for 3 or 5 days at the hospital and to comply with the follow-up schedule
Inclusion criteria for pregnant women (in addition to the above criteria except*):
- Gestational Age ≥ 14 weeks confirmed by ultrasound
- Singleton viable fetus
Exclusion criteria for non-pregnant women:
- Severe malaria or signs of severe malaria
- Medical conditions requiring concomitant drug treatment or transfer to a different hospital
- Intake of artemether-lumefantrine within the two previous 2 weeks
- Known allergy to the study drugs
- Previous participation in this study or current participation in other studies
Exclusion criteria for pregnant women (in addition to the above criteria):
- Signs of labour
- Fetal abnormalities identified by ultrasound
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Active Comparator: 3-day artemether-lumefantrine
Standard artemether-lumefantrine regimen (3-day treatment)
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|
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Experimental: 5-day artemether-lumefantrine
Artemether-lumefantrine extended regimen (5-day treatment)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Pharmacokinetics measures
Time Frame: 1 year
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Drug plasma concentration profiles for lumefantrine, artemether and dihydroartemisinin will be characterized for each patient.
Ten samples per patient will be taken at fixed and random times.
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1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Tolerability and safety measures
Time Frame: 2 years
|
Detection and assessment of adverse events during the therapy and in the follow-up period.
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2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Efficacy measures
Time Frame: 1 year
|
Therapeutic efficacy of the treatment will be assessed in the follow-up period according to WHO protocol for the evaluation of antimalarial efficacy.
Therapeutic responses will be correlated with drug concentration profiles.
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Nicholas P Day, MD PhD, University of Oxford
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2013
Primary Completion (Actual)
March 1, 2014
Study Registration Dates
First Submitted
August 1, 2013
First Submitted That Met QC Criteria
August 1, 2013
First Posted (Estimate)
August 6, 2013
Study Record Updates
Last Update Posted (Estimate)
March 26, 2014
Last Update Submitted That Met QC Criteria
March 24, 2014
Last Verified
March 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALN5P
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