MalariaPhase 3ALN5PNCT01916954
Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Malaria in Pregnancy
A Phase 3 study testing 3-day artemether-lumefantrine and 5-day artemether-lumefantrine in people with Malaria, run by University of Oxford at 1 site in Republic of the Congo.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Malaria
- What is being tested?
- 3-day artemether-lumefantrine and 5-day artemether-lumefantrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteRepublic of the Congo
- Study dates
- Jul 2013to Mar 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Republic of the Congo1 site
University of Kinshasa, Democratic Republic of Congo
Kinshasa
About this study
Official title: 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.
Read the 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.
- Conditions
- Malaria
- Being tested
- 3-day artemether-lumefantrine, 5-day artemether-lumefantrine
- Keywords
- Malaria, Pregnancy, Plasmodium falciparum
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-day artemether-lumefantrineDrug
5-day artemether-lumefantrineDrug
| Study group | Role | What they receive |
|---|---|---|
| 3-day artemether-lumefantrine | Active comparator | Standard artemether-lumefantrine regimen (3-day treatment) Receives: Drug: 3-day artemether-lumefantrine |
| 5-day artemether-lumefantrine | Experimental | Artemether-lumefantrine extended regimen (5-day treatment) Receives: Drug: 5-day artemether-lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics measures
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.
Measured: 1 year
Secondary outcomes (1)
Tolerability and safety measures
Detection and assessment of adverse events during the therapy and in the follow-up period.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kinshasa
- Responsible party
- Sponsor
- Investigators
- Nicholas P Day, MD PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01916954
- Sponsor's protocol ID
- ALN5P
- Acronym
- ALN5P
- Status last verified
- Mar 2014
- First submitted
- 1 Aug 2013
- Last updated
- 26 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Onyamboko MA, Hoglund RM, Lee SJ, Kabedi C, Kayembe D, Badjanga BB, Turner GDH, Jackson NV, Tarning J, McGready R, Nosten F, White NJ, Day NPJ, Fanello C. A Randomized Controlled Trial of Three- versus Five-Day Artemether-Lumefantrine Regimens for Treatment of Uncomplicated Plasmodium falciparum Malaria in Pregnancy in Africa. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01140-19. doi: 10.1128/AAC.01140-19. Print 2020 Feb 21.
PubMed 31818818
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Pregnant Women in the Democratic Republic of Congo
- ClinicalTrials.gov ID
- NCT01916954
- Acronym / sponsor ID
- ALN5P / ALN5P
- Conditions
- Malaria
- Keywords
- Malaria, Pregnancy, Plasmodium falciparum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Kinshasa
- Study start
- Jul 2013
- Primary completion
- Mar 2014 (actual)
- First posted
- 6 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 3-day artemether-lumefantrine | Active comparator | Drug: 3-day artemether-lumefantrineStandard artemether-lumefantrine regimen (3-day treatment) |
| 5-day artemether-lumefantrine | Experimental | Drug: 5-day artemether-lumefantrineArtemether-lumefantrine extended regimen (5-day treatment) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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*
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3-day artemether-lumefantrine | Drug | 3-day artemether-lumefantrine |
| 5-day artemether-lumefantrine | Drug | 5-day artemether-lumefantrine |
Primary outcome
Pharmacokinetics measures
Time frame: 1 year
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.
1 secondary outcome
Tolerability and safety measures
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2014.
- Derived from this study: PubMed 31818818Onyamboko MA, Hoglund RM, Lee SJ, Kabedi C, Kayembe D, Badjanga BB, Turner GDH, Jackson NV, Tarning J, McGready R, Nosten F, White NJ, Day NPJ, Fanello C. A Randomized Controlled Trial of Three- versus Five-Day Artemether-Lumefantrine Regimens for Treatment of Uncomplicated Plasmodium falciparum Malaria in Pregnancy in Africa. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01140-19. doi: 10.1128/AAC.01140-19. Print 2020 Feb 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas P Day, MD PhD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 3-day artemether-lumefantrine and 5-day artemether-lumefantrine in people with Malaria, run by University of Oxford at 1 site in Republic of the Congo.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Republic of the Congo. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics measures (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01916954, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2014.