Malaria, FalciparumNCT01326754
Efficacy of Artemether-lumefantrine, Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Malawi
A study testing Artemether-lumefantrine combination, Artesunate-amodiaquine combination and Dihydroartemisinin-piperaquine in people with Malaria, Falciparum, run by Centers for Disease Control and Prevention at 1 site in Malawi.
Trial summary
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. 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 combination, Artesunate-amodiaquine combination and Dihydroartemisinin-piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 498 participants
- Where
- 1 siteMalawi
- Study dates
- Aug 2011to Jun 2012
- Phase
- Interventional
- 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 2,000-200,000/µl asexual forms;
- presence of axillary or tympanic temperature ≥ 37.5 °C or oral or rectal temperature of ≥ 38 °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; and
- informed consent from the parent or guardian of the child.
Who cannot join
- presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1);
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition (defined as a child whose growth stand¬ard is below -3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm) and calculated using EpiInfo 2002 EpiNut calculator;
- 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, which may interfere with antimalarial pharmacokinetics;
- history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of the Dispersible Formulation of Artemether-lumefantrine, Co-formulated Artesunate-amodiaquine and Co-formulated Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Machinga District, Malawi
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 falling efficacy of sulfadoxine-pyrimethamine, the first-line treatment of uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007. 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. The change in policy was based primarily on efficacy data from other countries in sub-Saharan Africa. However, although both artemether-lumefantrine and artesunate-amodiaquine have been in use in Malawi since 2007, there are relatively few studies assessing their efficacy. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious.1 In addition, 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 (Kamija Phiri, personal communication).
Although, some Malawi-specific data on the in vivo efficacy of the standard formulation of artemether-lumefantrine exists, there are additional data that is needed to support the current policy and inform future policy decisions. In 2010 the NMCP has introduced the dispersible formulation of artemether-lumefantrine (Coartem-D™) for use as a first-line antimalarial in Malawi, due to the global unavailability of the standard formulation of artemether-lumefantrine from Novartis, the key supplier of the standard formulation of artemether-lumefantrine (Coartem™) in Malawi. In light of these developments, an assessment of the efficacy, safety and tolerability of the dispersible formulation of artemether-lumefantrine is warranted. In addition, the efficacy, safety and tolerability of co-formulated artesunate-amodiaquine, the current secondline treatment for uncomplicated malaria, has never been assessed in Malawi and should be evaluated. Lastly, dihydroartemisinin-piperaquine has recently been added to the new World Health Organization (WHO) guidelines for the treatment of uncomplicated malaria. This promising new antimalarial might have a role as a first-line or second-line antimalarial for the treatment of uncomplicated malaria, but there are no efficacy and safety data from Malawi. This knowledge gap needs to be addressed to help inform policy makers about the potential role of dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Malawi.
Read more
Objective: Efficacy and safety of the dispersible formulation of artemether-lumefantrine, co-formulated artesunate-amodiaquine and co-formulated dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga District Hospital- Malawi
Methods: An antimalarial drug efficacy trial will be conducted in Malawi. The participants will be febrile people 6-59 months old with confirmed uncomplicated P. falciparum infection. Patients will be sequentially allocated 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; or co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug effi¬cacy. The study will be conducted from January to December, 2011. The results of this study will be used to assist the Ministry of Health in Malawi in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria.
- Conditions
- Malaria, Falciparum
- Being tested
- Artemether-lumefantrine combination, Artesunate-amodiaquine combination, Dihydroartemisinin-piperaquine
- 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 combinationDrug
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
Artesunate-amodiaquine combinationDrug
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
Dihydroartemisinin-piperaquineDrug
Co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days
| Study group | Role | What they receive |
|---|---|---|
| Artemether-lumefantrine | Other | Not described Receives: Drug: Artemether-lumefantrine combination |
| Artesunate-amodiaquine | Other | Not described Receives: Drug: Artesunate-amodiaquine combination |
| Dihydroartemisinin-piperaquine | Other | Not described Receives: Drug: Dihydroartemisinin-piperaquine |
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 42, 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: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2011 (estimated)
- Study startAug 2011
- Primary completionJun 2012
- Study completionJun 2012
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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 498 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
- Principal investigator, Jacek Skarbinski, Centers for Disease Control and Prevention
- Investigators
- Jacek Skarbinski, MD, Principal investigator, Centers for Disease Control and PreventionDon Mathanga, MBBS PhD, Principal investigator, Kamuzu University of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01326754
- Sponsor's protocol ID
- CDC-CGH-6029
- Status last verified
- Feb 2013
- First submitted
- 30 Mar 2011
- Last updated
- 25 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of the Dispersible Formulation of Artemether-lumefantrine, Co-formulated Artesunate-amodiaquine and Co-formulated Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Machinga District, Malawi
- ClinicalTrials.gov ID
- NCT01326754
- Acronym / sponsor ID
- CDC-CGH-6029
- Conditions
- Malaria, Falciparum
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 498 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Kamuzu University of Health Sciences
- Study start
- Aug 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 31 Mar 2011 (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.
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 falling efficacy of sulfadoxine-pyrimethamine, the first-line treatment of uncomplicated malaria from 1993 to 2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines in 2007. 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. The change in policy was based primarily on efficacy data from other countries in sub-Saharan Africa. However, although both artemether-lumefantrine and artesunate-amodiaquine have been in use in Malawi since 2007, there are relatively few studies assessing their efficacy. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine was found to be efficacious.1 In addition, 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 (Kamija Phiri, personal communication).
Although, some Malawi-specific data on the in vivo efficacy of the standard formulation of artemether-lumefantrine exists, there are additional data that is needed to support the current policy and inform future policy decisions. In 2010 the NMCP has introduced the dispersible formulation of artemether-lumefantrine (Coartem-D™) for use as a first-line antimalarial in Malawi, due to the global unavailability of the standard formulation of artemether-lumefantrine from Novartis, the key supplier of the standard formulation of artemether-lumefantrine (Coartem™) in Malawi. In light of these developments, an assessment of the efficacy, safety and tolerability of the dispersible formulation of artemether-lumefantrine is warranted. In addition, the efficacy, safety and tolerability of co-formulated artesunate-amodiaquine, the current secondline treatment for uncomplicated malaria, has never been assessed in Malawi and should be evaluated. Lastly, dihydroartemisinin-piperaquine has recently been added to the new World Health Organization (WHO) guidelines for the treatment of uncomplicated malaria. This promising new antimalarial might have a role as a first-line or second-line antimalarial for the treatment of uncomplicated malaria, but there are no efficacy and safety data from Malawi. This knowledge gap needs to be addressed to help inform policy makers about the potential role of dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Malawi.
Objective: Efficacy and safety of the dispersible formulation of artemether-lumefantrine, co-formulated artesunate-amodiaquine and co-formulated dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria at Machinga District Hospital- Malawi
Methods: An antimalarial drug efficacy trial will be conducted in Malawi. The participants will be febrile people 6-59 months old with confirmed uncomplicated P. falciparum infection. Patients will be sequentially allocated 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; or co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days. Clinical and parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug effi¬cacy. The study will be conducted from January to December, 2011. The results of this study will be used to assist the Ministry of Health in Malawi in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Artemether-lumefantrine | Other | Drug: Artemether-lumefantrine combination |
| Artesunate-amodiaquine | Other | Drug: Artesunate-amodiaquine combination |
| Dihydroartemisinin-piperaquine | Other | Drug: Dihydroartemisinin-piperaquine |
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 2,000-200,000/µl asexual forms;
- presence of axillary or tympanic temperature ≥ 37.5 °C or oral or rectal temperature of ≥ 38 °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 under 5 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1);
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition (defined as a child whose growth stand¬ard is below -3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm) and calculated using EpiInfo 2002 EpiNut calculator;
- 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, which 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 combinationDispersible 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 | Drug | Artemether-lumefantrine |
| Artesunate-amodiaquine combinationCo-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day amodiaquine once a day for 3 days | Drug | Artesunate-amodiaquine |
| Dihydroartemisinin-piperaquineCo-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days | Drug | Dihydroartemisinin-piperaquine |
Primary outcome
Adequate clinical and parasitological response (ACPR)
Time frame: 42 days
Absence of parasitaemia on day 42, 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 25 Feb 2013.
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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.
Jacek Skarbinski, MD principal investigator
Centers for Disease Control and Prevention
Don Mathanga, MBBS PhD principal investigator
Kamuzu University of Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Artemether-lumefantrine combination, Artesunate-amodiaquine combination and Dihydroartemisinin-piperaquine 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 25 Feb 2013. 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.
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: 42 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 25 Feb 2013.