MalariaPhase 4NCT01976780
In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy
A Phase 4 study testing Artesunate, Artemether Lumefantrine and Mefloquine in people with Malaria, run by Global Emerging Infections Surveillance and Response System at 1 site in Kenya.
Trial summary
This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ). Read more about this study
- Who is it for?
- Ages 6 months to 65 years
- Conditions the study is for
- Malaria
- What is being tested?
- Artesunate, Artemether Lumefantrine and Mefloquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteKenya
- Study dates
- Jun 2013to Dec 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 months to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adult/child aged between 6 months and 65 years inclusive (minimum weight 11kg), presenting with a measured temperature of ≥37.5 C, or history of fever within 24 hours prior to presentation
- Mono-infection with Plasmodium falciparum
- Baseline parasitemia of 2000 - 200,000 asexual parasites/µl
- Ability to provide informed consent
- Willingness and ability to comply with the study protocol for the duration of the study
- Willingness to remain in the hospital for 3 days
Who cannot join
- Presence of signs of severe malaria as defined by WHO
- Presence of severe anemia, defined as hemoglobin level below 6 g/dl
- Presence of mixed Plasmodium infection, or mono-infection of non-falciparum Plasmodium
- Inability to take oral medication
- History of allergy or contraindications to the study treatments
- Lactating or pregnant females
- Any condition that the investigator feels will result in an unfavorable outcome should the potential subject participate in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy in Kisumu County, Western Kenya
This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ).
Read the detailed description
Data generated by this study will provide a snapshot of the current situation regarding P. falciparum sensitivity to ACTs in Western Kenya. By having subjects in one of the study arms receive artesunate and then the partner drug after completion of the artemisinin phase will enable the accurate evaluation of the artemisinin derivative without the confounding influence of the partner drug. Sequential administration of the components of an ACT drug is recognized by the WHO as one of the ways in which ACTs can be administered. There will be close follow-up of the subjects throughout the duration of the study, and as such, subjects who fail to respond adequately will receive prompt rescue treatment. Since it is largely expected that most subjects in Western Kenya will have satisfactory responses to ACTs, data from this study will provide baseline information regarding parasite characteristics when compared to data from Thailand, an area that has reported resistance to ACTs. This, in turn, will potentially enable the identification of key markers, both in the host and the parasite, that may assist in the early detection of resistance, and also to better understand the development of resistance to ACTs. As such, the data generated from this study, both on its own and when compared to and pooled with data from similar studies that will be conducted in Peru and Thailand, will potentially inform both local and international policy regarding ACT use for the treatment of uncomplicated P. falciparum malaria.
- Conditions
- Malaria
- Being tested
- Artesunate, Artemether Lumefantrine, Mefloquine
- Keywords
- Malaria, P. falciparum mono infection, Early Treatment Failure, Late Treatment Failure
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArtesunateDrug
Also called AS
Artemether LumefantrineDrug
Also called AL
MefloquineDrug
Also called MQ
| Study group | Role | What they receive |
|---|---|---|
| AS/MQ | Active comparator | Treatment of P.falciparum mono-infection with 4 mg/kg of Artesunate daily for three days followed by 25mg/kg of Mefloquine split over two days. Receives: Drug: Artesunate; Drug: Mefloquine |
| AL | Active comparator | Treatment of P. falciparum mono-infection with Artemether Lumefantrine administered at the standard dosage according to pre-defined weight bands (5-14 kg: 1 tablet; 15-24 kg: 2 tablets; 25-34 kg: 3 tablets; and > 34 kg: 4 tablets) given twice a day for 3 days. Receives: Drug: Artemether Lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasitological clearance rates by microscopy
Clearance rates for the first 72 hour period after first ACT dose in patients with uncomplicated P. falciparum malaria
Measured: 72 hours
Secondary outcomes (7)
Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR)
PCR adjusted clearance rates for the first 72 hours after first ACT dose in patients with uncomplicated P. falciparum malaria
Measured: 72 hours
PCR-adjusted treatment efficacy of AL and AS/MQ
Measured: 42 days
Antimalarial drug sensitivity responses and molecular genotyping
Correlate clinical outcomes with results of above tests
Measured: 42 days
Identify common specific genetic determinants of artemisinin resistance derived from parasite populations
Measured: 42 days
Gametocyte carriage in patients with uncomplicated malaria after treatment
Measured: 42 days
Catalog parasite samples
Correlated to clinical datasets to longitudinally track resistance trends
Measured: 42 days
Pharmacokinetic parameters associated with ACT 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 posted6 Nov 2013 (estimated)
- Study startJun 2013
- Primary completionDec 2014
- Study completionDec 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.
- 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
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Emerging Infections Surveillance and Response System
- Sponsor type
- US federal agency
- Collaborators
- United States Army Medical Unit - Kenya, Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- James F Cummings, MD, Study chair, GEISBen Andagalu, MD, Principal investigator, Kenya Medical Research Institute/Walter Reed Project
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01976780
- Sponsor's protocol ID
- WRAIR1935
- Status last verified
- May 2017
- First submitted
- 25 Oct 2013
- Last updated
- 11 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Odhiambo G, Bergmann-Leitner E, Maraka M, Wanjala CNL, Duncan E, Waitumbi J, Andagalu B, Jura WGZO, Dutta S, Angov E, Ogutu BR, Kamau E, Ochiel D. Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya. J Infect Dis. 2019 May 24;219(12):1969-1979. doi: 10.1093/infdis/jiz027.
PubMed 30649381
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy in Kisumu County, Western Kenya
- ClinicalTrials.gov ID
- NCT01976780
- Acronym / sponsor ID
- WRAIR1935
- Conditions
- Malaria
- Keywords
- Malaria, P. falciparum mono infection, Early Treatment Failure, Late Treatment Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Global Emerging Infections Surveillance and Response SystemUS federal agency
- Collaborators
- United States Army Medical Unit - Kenya, Walter Reed Army Institute of Research (WRAIR)
- Study start
- Jun 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 6 Nov 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.
This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ).
Detailed description
Data generated by this study will provide a snapshot of the current situation regarding P. falciparum sensitivity to ACTs in Western Kenya. By having subjects in one of the study arms receive artesunate and then the partner drug after completion of the artemisinin phase will enable the accurate evaluation of the artemisinin derivative without the confounding influence of the partner drug. Sequential administration of the components of an ACT drug is recognized by the WHO as one of the ways in which ACTs can be administered. There will be close follow-up of the subjects throughout the duration of the study, and as such, subjects who fail to respond adequately will receive prompt rescue treatment. Since it is largely expected that most subjects in Western Kenya will have satisfactory responses to ACTs, data from this study will provide baseline information regarding parasite characteristics when compared to data from Thailand, an area that has reported resistance to ACTs. This, in turn, will potentially enable the identification of key markers, both in the host and the parasite, that may assist in the early detection of resistance, and also to better understand the development of resistance to ACTs. As such, the data generated from this study, both on its own and when compared to and pooled with data from similar studies that will be conducted in Peru and Thailand, will potentially inform both local and international policy regarding ACT use for the treatment of uncomplicated P. falciparum malaria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AS/MQ | Active comparator | Drug: Artesunate, Drug: MefloquineTreatment of P.falciparum mono-infection with 4 mg/kg of Artesunate daily for three days followed by 25mg/kg of Mefloquine split over two days. |
| AL | Active comparator | Drug: Artemether LumefantrineTreatment of P. falciparum mono-infection with Artemether Lumefantrine administered at the standard dosage according to pre-defined weight bands (5-14 kg: 1 tablet; 15-24 kg: 2 tablets; 25-34 kg: 3 tablets; and > 34 kg: 4 tablets) given twice a day for 3 days. |
Who may qualify
- Ages
- 6 months to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Adult/child aged between 6 months and 65 years inclusive (minimum weight 11kg), presenting with a measured temperature of ≥37.5 C, or history of fever within 24 hours prior to presentation
- Mono-infection with Plasmodium falciparum
- Baseline parasitemia of 2000 - 200,000 asexual parasites/µl
- Ability to provide informed consent
- Willingness and ability to comply with the study protocol for the duration of the study
Key exclusion criteria (7 listed)
- Presence of signs of severe malaria as defined by WHO
- Presence of severe anemia, defined as hemoglobin level below 6 g/dl
- Presence of mixed Plasmodium infection, or mono-infection of non-falciparum Plasmodium
- Inability to take oral medication
- History of allergy or contraindications to the study treatments
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 |
|---|---|---|
| ArtesunateAlso: AS | Drug | AS/MQ |
| Artemether LumefantrineAlso: AL | Drug | AL |
| MefloquineAlso: MQ | Drug | AS/MQ |
Primary outcome
Parasitological clearance rates by microscopy
Time frame: 72 hours
Clearance rates for the first 72 hour period after first ACT dose in patients with uncomplicated P. falciparum malaria
7 secondary outcomes
Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR)
Time frame: 72 hours
PCR-adjusted treatment efficacy of AL and AS/MQ
Time frame: 42 days
Antimalarial drug sensitivity responses and molecular genotyping
Time frame: 42 days
Identify common specific genetic determinants of artemisinin resistance derived from parasite populations
Time frame: 42 days
Gametocyte carriage in patients with uncomplicated malaria after treatment
Time frame: 42 days
Catalog parasite samples
Time frame: 42 days
Pharmacokinetic parameters associated with ACT failure
Time frame: 42 days
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 11 May 2017.
- Derived from this study: PubMed 30649381Odhiambo G, Bergmann-Leitner E, Maraka M, Wanjala CNL, Duncan E, Waitumbi J, Andagalu B, Jura WGZO, Dutta S, Angov E, Ogutu BR, Kamau E, Ochiel D. Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya. J Infect Dis. 2019 May 24;219(12):1969-1979. doi: 10.1093/infdis/jiz027.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
James F Cummings, MD study chair
GEIS
Ben Andagalu, MD principal investigator
Kenya Medical Research Institute/Walter Reed Project
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 Artesunate, Artemether Lumefantrine and Mefloquine in people with Malaria, run by Global Emerging Infections Surveillance and Response System at 1 site in Kenya.
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 6 inclusion and 7 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 11 May 2017. 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 Kenya. 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?
Parasitological clearance rates by microscopy (time frame: 72 hours). 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 NCT01976780, 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 11 May 2017.