MALARIA, FALCIPARUMPhase 4NCT02637128
In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated P. Falciparum Malaria
A Phase 4 study testing artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) in people with MALARIA, FALCIPARUM, run by Centers for Disease Control and Prevention at 1 site in Malawi.
Trial summary
This study was designed to determine the efficacy of both artemether-lumefantrine and artesunate-amodiaquine (but not to compare the efficacies of the two drugs) for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi. Read more about this study
- Who is it for?
- Ages 6 to 59 months
- Conditions the study is for
- MALARIA, FALCIPARUM
- What is being tested?
- artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 452 participants
- Where
- 1 siteMalawi
- Study dates
- Mar 2014to Jul 2014
- Phase
- Phase 4
- 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 6 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- age between 6 to 59 months
- mono-infection with P. falciparum detected by microscopy
- parasitaemia of 1,000-200,000/µl asexual forms
- presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h
- ability to swallow oral medication
- ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule
- informed consent from the parent or guardian of the child
Who cannot join
- presence of general danger signs in children aged 6-59 months or signs of severe falciparum malaria according to the definitions of World Health Organization
- mixed or mono-infection with another Plasmodium species detected by microscopy
- presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score)
- presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS)
- regular medication that may interfere with antimalarial pharmacokinetics
- history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatments
Trial locations and contacts
1 site in 1 country.
Malawi1 site
Malaria Alert Center, University of Malawi College of Medicine, Blantyre, Malawi
Blantyre
About this study
Official title: In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated Plasmodium Falciparum Malaria in Malawi, 2014
This study was designed to determine the efficacy of both artemether-lumefantrine and artesunate-amodiaquine (but not to compare the efficacies of the two drugs) for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi.
Read the detailed description
Background: Malaria is a cause of substantial morbidity and mortality in Malawi. Prompt and effective treatment of uncomplicated malaria remains a key strategy to reduce the public health burden of malaria. Due to the rising resistance to and declining efficacy of sulfadoxine-pyrimethamine, the first-line treatment for uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007 and again in 2013. The revised treatment guidelines recommend artemether-lumefantrine as the first-line treatment for uncomplicated malaria and artesunate-amodiaquine as a second-line treatment for uncomplicated malaria. Data from Malawi suggests that these drugs remain efficacious. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious. A more recent assessment of artemether-lumefantrine in vivo efficacy conducted in six sites in Malawi in 2009 also suggests that the standard formulation artemether-lumefantrine remains highly efficacious. In addition, both the dispersible formulation of artemether-lumefantrine (Coartem-D™) and artesunate-amodiaquine were extremely well tolerated and safe in studies conducted in Malawi as well as in other Sub-Saharan African countries. Given the potential for development of parasite resistance, it is imperative to continue to monitor the efficacy of these drugs as long as they remain the recommended treatment regimens.
Objective: Determine the efficacy of artemether-lumefantrine and co-formulated artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi
Methods: A randomized drug efficacy trial will be conducted in Malawi. The trial will include 453 febrile children 6-59 months old with confirmed uncomplicated P. falciparum infection, seeking care at Machinga, Nkhotakota, and Karonga District Hospitals; 151 patients will be enrolled at each site (113 for artemether-lumefantrine and 38 for co-formulated artesunate-amodiaquine). Patients will be randomized to receive treatment with either the dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.
- Conditions
- MALARIA, FALCIPARUM
- Being tested
- artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ)
- Keywords
- MALARIA, FALCIPARUM, MALAWI, ARTEMETHER-LUMEFANTRINE, ARTESUNATE-AMODIAQUINE
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
artemether-lumefantrine (AL)Drug
Also called Coartem
Dispersible formulation of artemether-lumefantrine (Coartem-D™; 20mg artemether/120mg lumefantrine per tablet, Novartis, Switzerland) administered twice a day for 3 days according to manufacturer recommended dosing for weight
artesunate-amodiaquine (ASAQ)Drug
Also called Coarsucam
Co-formulated artesunate-amodiaquine (25mg artesunate/67.5mg amodiaquine and 50mg artesunate/135mg amodiaquine tablets) administered once a day for 3 days, according to manufacturer recommended dosing for weight
| Study group | Role | What they receive |
|---|---|---|
| artemether-lumefantrine (AL) | Experimental | 20mg artemether/120 mg lumefantrine per tablet, Coartem-D™; Novartis, Basel, Switzerland administered following manufacturer's prescribed weight-based dosing, twice daily for 3 days.
5-14 kg: 1 tablet; 15-24: 2 tablets; 25-34 kg: 3 tablets; >34 kg: 4 tablets per dose Receives: Drug: artemether-lumefantrine (AL) |
| artesunate-amodiaquine (ASAQ) | Experimental | 25mg artesunate/67.5 mg amodiaquine or 50 mg artesunate/135mg amodiaquine per tablet, Coarsucam™; Sanofi-Aventis, Paris, France administered following manufacturer's prescribed weight-based dosing, once daily for 3 days 4.5-8.9 kg: 1 25mg/67.5 mg tablet; 9-17.9 kg: 1 50mg/135 mg tablet; 18-35.9 kg 2 50mg/135 tablets; >36 kg: 4 50mg/135mg tablets per dose Receives: Drug: artesunate-amodiaquine (ASAQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adequate clinical and parasitological response (ACPR)
Absence of parasitaemia on day 28, assessed by microscopy, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2015 (estimated)
- Study startMar 2014
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MALARIA, FALCIPARUMStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Kamuzu University of Health Sciences
- Responsible party
- Sponsor
- Investigators
- Don P Mathanga, MBBS, PhD, Principal investigator, 1. Malaria Alert Centre (MAC), University of Malawi College of Medicine, Blantyre, Malawi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02637128
- Sponsor's protocol ID
- Malawi TES 2014
- Status last verified
- Dec 2015
- First submitted
- 17 Dec 2015
- Last updated
- 22 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated Plasmodium Falciparum Malaria in Malawi, 2014
- ClinicalTrials.gov ID
- NCT02637128
- Acronym / sponsor ID
- Malawi TES 2014
- Conditions
- MALARIA, FALCIPARUM
- Keywords
- MALARIA, FALCIPARUM, MALAWI, ARTEMETHER-LUMEFANTRINE, ARTESUNATE-AMODIAQUINE
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 452 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Kamuzu University of Health Sciences
- Study start
- Mar 2014
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 22 Dec 2015 (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.
This study was designed to determine the efficacy of both artemether-lumefantrine and artesunate-amodiaquine (but not to compare the efficacies of the two drugs) for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi.
Detailed description
Background: Malaria is a cause of substantial morbidity and mortality in Malawi. Prompt and effective treatment of uncomplicated malaria remains a key strategy to reduce the public health burden of malaria. Due to the rising resistance to and declining efficacy of sulfadoxine-pyrimethamine, the first-line treatment for uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007 and again in 2013. The revised treatment guidelines recommend artemether-lumefantrine as the first-line treatment for uncomplicated malaria and artesunate-amodiaquine as a second-line treatment for uncomplicated malaria. Data from Malawi suggests that these drugs remain efficacious. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious. A more recent assessment of artemether-lumefantrine in vivo efficacy conducted in six sites in Malawi in 2009 also suggests that the standard formulation artemether-lumefantrine remains highly efficacious. In addition, both the dispersible formulation of artemether-lumefantrine (Coartem-D™) and artesunate-amodiaquine were extremely well tolerated and safe in studies conducted in Malawi as well as in other Sub-Saharan African countries. Given the potential for development of parasite resistance, it is imperative to continue to monitor the efficacy of these drugs as long as they remain the recommended treatment regimens.
Objective: Determine the efficacy of artemether-lumefantrine and co-formulated artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District Hospitals- Malawi
Methods: A randomized drug efficacy trial will be conducted in Malawi. The trial will include 453 febrile children 6-59 months old with confirmed uncomplicated P. falciparum infection, seeking care at Machinga, Nkhotakota, and Karonga District Hospitals; 151 patients will be enrolled at each site (113 for artemether-lumefantrine and 38 for co-formulated artesunate-amodiaquine). Patients will be randomized to receive treatment with either the dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| artemether-lumefantrine (AL) | Experimental | Drug: artemether-lumefantrine (AL)20mg artemether/120 mg lumefantrine per tablet, Coartem-D™; Novartis, Basel, Switzerland administered following manufacturer's prescribed weight-based dosing, twice daily for 3 days. 5-14 kg: 1 tablet; 15-24: 2 tablets; 25-34 kg: 3 tablets; >34 kg: 4 tablets per dose |
| artesunate-amodiaquine (ASAQ) | Experimental | Drug: artesunate-amodiaquine (ASAQ)25mg artesunate/67.5 mg amodiaquine or 50 mg artesunate/135mg amodiaquine per tablet, Coarsucam™; Sanofi-Aventis, Paris, France administered following manufacturer's prescribed weight-based dosing, once daily for 3 days 4.5-8.9 kg: 1 25mg/67.5 mg tablet; 9-17.9 kg: 1 50mg/135 mg tablet; 18-35.9 kg 2 50mg/135 tablets; >36 kg: 4 50mg/135mg tablets per dose |
Who may qualify
- Ages
- 6 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- age between 6 to 59 months
- mono-infection with P. falciparum detected by microscopy
- parasitaemia of 1,000-200,000/µl asexual forms
- presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h
- ability to swallow oral medication
Key exclusion criteria (6 listed)
- presence of general danger signs in children aged 6-59 months or signs of severe falciparum malaria according to the definitions of World Health Organization
- mixed or mono-infection with another Plasmodium species detected by microscopy
- presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score)
- presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS)
- regular medication that may interfere with antimalarial pharmacokinetics
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 |
|---|---|---|
| artemether-lumefantrine (AL)Also: CoartemDispersible formulation of artemether-lumefantrine (Coartem-D™; 20mg artemether/120mg lumefantrine per tablet, Novartis, Switzerland) administered twice a day for 3 days according to manufacturer recommended dosing for weight | Drug | artemether-lumefantrine (AL) |
| artesunate-amodiaquine (ASAQ)Also: CoarsucamCo-formulated artesunate-amodiaquine (25mg artesunate/67.5mg amodiaquine and 50mg artesunate/135mg amodiaquine tablets) administered once a day for 3 days, according to manufacturer recommended dosing for weight | Drug | artesunate-amodiaquine (ASAQ) |
Primary outcome
Adequate clinical and parasitological response (ACPR)
Time frame: 28 days
Absence of parasitaemia on day 28, assessed by microscopy, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure
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 22 Dec 2015.
- Individual participant dataSharing planned: Undecided
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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.
Don P Mathanga, MBBS, PhD principal investigator
1. Malaria Alert Centre (MAC), University of Malawi College of Medicine, Blantyre, Malawi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) in people with MALARIA, FALCIPARUM, run by Centers for Disease Control and Prevention at 1 site in Malawi.
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 7 inclusion and 6 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 22 Dec 2015. 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 Malawi. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Adequate clinical and parasitological response (ACPR) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Dec 2015.