MalariaPhase 4NCT02052323
Harmonized AS/MQ Efficacy Study - Thailand
A Phase 4 study testing Artesunate/mefloquine (AS/MQ) in people with Malaria, run by Armed Forces Research Institute of Medical Sciences, Thailand at 1 site in Thailand.
Trial summary
The purposes of this study is to determine parasitological clearance rates by microscopy for the 72-hour period after first artesunate dose in subjects with uncomplicated P. falciparum malaria. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Malaria
- What is being tested?
- Artesunate/mefloquine (AS/MQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteThailand
- Study dates
- Oct 2013to Oct 2015
- 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 5 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Thai or non-Thai, otherwise healthy, male or female, aged from 5 years to 65 years inclusive
- Acute uncomplicated P. falciparum malaria monoinfection, confirmed by positive blood smear
- Asexual P. falciparum parasitaemia of 1,000 to 200,000 parasites/µL, confirmed on a thin or thick blood film
- Fever defined as ≥ 38.0°C tympanic temperature (or equivalent) or a history of fever within the last 24 hours
- Willingness to participate in the study as evidenced by written informed consent from the subject or parent/guardian (for children), and by assent (for children)
Who cannot join
- Severe malaria as defined by WHO criteria (reference WHO 2012)
- Inability to eat or drink, inability to tolerate oral antimalarial medication, recent history of seizures (one or more in the previous 24 hours), altered level of consciousness, inability to sit or stand
- Mixed species asexual stage malaria infection as determined by microscopy
- Recent antimalarial treatment, defined as a clear history of any antimalarial medication taken within the previous 7 days; or a clear history of mefloquine within previous 4 weeks
- History of splenectomy
- Pregnancy or nursing mother
- Known hypersensitivity to artesunate, mefloquine or primaquine
- PI determines that it is in the best interests of the subject not to participate in the trial
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Kwai River Christian Hospital in Sangklaburi
Thong Pha Phum, Kanchanaburi, 71240
About this study
Official title: Study to Determine the Efficacy of Artesunate-mefloquine Combination Therapy for the Treatment of Uncomplicated P. Falciparum Malaria in Thailand
The purposes of this study is to determine parasitological clearance rates by microscopy for the 72-hour period after first artesunate dose in subjects with uncomplicated P. falciparum malaria.
Read the detailed description
Project Summary
Objectives
Primary Objective
- To determine parasitological clearance rates by microscopy for the 72-hour period after first artesunate dose in subjects with uncomplicated P. falciparum malaria
Secondary Objectives
2.1. To describe clinical and parasitological outcomes for subjects with uncomplicated P. falciparum malaria treated with AS-MQ administered sequentially.
2.2. To measure the gametocyte carriage rate in subjects with uncomplicated malaria before and after treatment.
2.3. To monitor drug levels associated with artesunate-mefloquine treatment failure.
2.4. To determine in vitro drug sensitivity profiles for fresh parasites from malaria-infected subjects prior to artesunate-mefloquine treatment and at the time of parasite recurrence.
2.5. To identify specific genetic determinants of artemisinin resistance derived from parasite populations.
2.6. To correlate clinical outcomes from the in vivo study with in vitro antimalarial drug sensitivity responses and molecular genotyping.
2.7. To compare P. falciparum malaria artemisinin resistance genotypes at three sites in three continents, using clinical and parasitological outcomes, in vitro drug sensitivity profiles, and molecular markers generated using harmonized methodologies.
2.8. To determine the contribution of host immunity to parasitological and clinical outcomes.
2.9. To create a catalog of parasite samples closely correlated to clinical datasets to longitudinally track resistance trends.
Subject Population
Subjects aged 5-65 years, who meet study entry criteria will be drawn from the local community.
Study Site
The study will be based at the Kwai River Christian Hospital (KRCH) in Sangklaburi District, Kanchanaburi Province, Thailand, which is located about 360km northwest of Bangkok near the Thailand-Myanmar border. Additional sites in Thailand, including in Sai Yok District, Kanchanaburi Province, may be added if enrolment at Sangklaburi is insufficient.
Number of Subjects
Up to 100 subjects will be enrolled to ensure a minimum of 59 subjects complete all study activities. This will allow for 40% subjects dropping out or being otherwise unevaluable. Up to 200 subjects may be screened to achieve the required number of evaluable subjects. A subject is considered evaluable at 72 hours from the commencement of artesunate treatment or once asexual parasites have been cleared from peripheral blood based on microscopy, whichever is longer.
Treatment
The antimalarial drug regimen being evaluated is: artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours; plus mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours; plus primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours.
Study Design and Methodology
This is an open-label, single-arm evaluation of AS-MQ combination for the treatment of uncomplicated P. falciparum malaria. Subjects will remain as in-patients until completion of antimalarial treatment and will then be followed up weekly to 42 days.
Study Endpoints
Primary Endpoint
- Parasite clearance rate as defined by the slope of the linear portion of the logarithm parasite clearance curve using microscopy to determine parasitemia
Secondary Endpoints
2.1. A description of the clinical and parasitological features of uncomplicated malaria in this setting (composite endpoint), including:
- Parasite clearance rate during the first 72 hours after artesunate administration as defined by the slope of the linear portion of the logarithm parasite clearance curve using qPCR to determine parasitemia
- Parasite reduction ratios at 24 and 48 hours assessed by microscopy and qPCR
- Time for parasite count to fall to 50%, 90%, 99% and 100% of initial parasite density
- Fever clearance time (i.e. the time taken for temperature to fall below 38.0˚C (tympanic method) or below 37.5˚C (axillary method) and remain there for at least 24 hours)
- 42-day PCR-adjusted treatment efficacy using World Health Organization classification of outcome.
2.2. Gametocyte carriage rates assessed in person weeks (up to 42 days) 2.3. Plasma levels of AS, DHA and MQ at selected time points 2.4. In vitro IC50, IC90, IC99 P. falciparum responses to a panel of antimalarial drugs, including dihydroartemisinin (DHA) and mefloquine.
2.5. Parasite molecular markers of drug resistance as determined by GWAS, SNP analysis and other genotyping methodologies 2.6. A detailed characterization of drug-resistant malaria using integrated endpoints above, including clinical, in vitro and molecular 2.7. Comparison of clinical and parasitological outcomes and in vitro and molecular features of parasites between harmonized sites in Kenya and Peru.
2.8. Identification of host factors that correlate with slow parasite clearance and other clinical outcomes 2.9. Creation of a well-characterised catalog of malaria parasites for future research
- Conditions
- Malaria
- Being tested
- Artesunate/mefloquine (AS/MQ)
- Keywords
- P.f Malaria, Artemisinin resistance, ACT 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.
Artesunate/mefloquine (AS/MQ)Drug
Also called Mequin
- artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours
- mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours
- primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours
| Study group | Role | What they receive |
|---|---|---|
| artesunate/mefloquine (AS/MQ) | Experimental | The antimalarial drug regimen being evaluated is: artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours; plus mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours; plus primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours Receives: Drug: Artesunate/mefloquine (AS/MQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasite clearance rate
Parasite clearance rate as defined by the slope of the linear portion of the logarithm parasite clearance curve using microscopy to determine parasitemia
Measured: one year
Secondary outcomes (1)
Number of patients with prolonged parasite clearance times, adequate drug levels and positive molecular markers of parasite resistance.
- Parasite clearance rate during the first 72 hours after artesunate administration as defined by the slope of the linear portion of the logarithm parasite clearance curve using qPCR
- Parasite reduction ratios at 24 and 48 hours assessed by microscopy and qPCR
- Time for parasite count to fall to 50%, 90%, 99% and 100% of initial parasite density
- Fever clearance time
- 42-day PCR-adjusted treatment efficacy
- Gametocyte carriage rates
- Plasma levels of AS, DHA and MQ at selected time points
- In vitro IC50, IC90, IC99 P. falciparum responses to a panel of antimalarial drugs, including dihydroartemisinin (DHA) and mefloquine
- Parasite molecular markers of drug resistance as determined by GWAS, SNP analysis and other genotyping methodologies
- A detailed characterization of drug-resistant malaria using integrated endpoints above, including clinical, in vitro and molecular
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startOct 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Armed Forces Research Institute of Medical Sciences, Thailand
- Sponsor type
- Other government
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Global Emerging Infections Surveillance and Response System
- Responsible party
- Sponsor
- Investigators
- Krisada Jongsakul, MD, Principal investigator, Armed Forces Research Institute of Medical Sciences, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02052323
- Sponsor's protocol ID
- WRAIR2017
- Status last verified
- Jan 2016
- First submitted
- 7 Jan 2014
- Last updated
- 25 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Determine the Efficacy of Artesunate-mefloquine Combination Therapy for the Treatment of Uncomplicated P. Falciparum Malaria in Thailand
- ClinicalTrials.gov ID
- NCT02052323
- Acronym / sponsor ID
- WRAIR2017
- Conditions
- Malaria
- Keywords
- P.f Malaria, Artemisinin resistance, ACT treatment failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Armed Forces Research Institute of Medical Sciences, ThailandOther government
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Global Emerging Infections Surveillance and Response System
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 3 Feb 2014 (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.
The purposes of this study is to determine parasitological clearance rates by microscopy for the 72-hour period after first artesunate dose in subjects with uncomplicated P. falciparum malaria.
Detailed description
Project Summary
Objectives
Primary Objective
- To determine parasitological clearance rates by microscopy for the 72-hour period after first artesunate dose in subjects with uncomplicated P. falciparum malaria
Secondary Objectives
2.1. To describe clinical and parasitological outcomes for subjects with uncomplicated P. falciparum malaria treated with AS-MQ administered sequentially.
2.2. To measure the gametocyte carriage rate in subjects with uncomplicated malaria before and after treatment.
2.3. To monitor drug levels associated with artesunate-mefloquine treatment failure.
2.4. To determine in vitro drug sensitivity profiles for fresh parasites from malaria-infected subjects prior to artesunate-mefloquine treatment and at the time of parasite recurrence.
2.5. To identify specific genetic determinants of artemisinin resistance derived from parasite populations.
2.6. To correlate clinical outcomes from the in vivo study with in vitro antimalarial drug sensitivity responses and molecular genotyping.
2.7. To compare P. falciparum malaria artemisinin resistance genotypes at three sites in three continents, using clinical and parasitological outcomes, in vitro drug sensitivity profiles, and molecular markers generated using harmonized methodologies.
2.8. To determine the contribution of host immunity to parasitological and clinical outcomes.
2.9. To create a catalog of parasite samples closely correlated to clinical datasets to longitudinally track resistance trends.
Subject Population
Subjects aged 5-65 years, who meet study entry criteria will be drawn from the local community.
Study Site
The study will be based at the Kwai River Christian Hospital (KRCH) in Sangklaburi District, Kanchanaburi Province, Thailand, which is located about 360km northwest of Bangkok near the Thailand-Myanmar border. Additional sites in Thailand, including in Sai Yok District, Kanchanaburi Province, may be added if enrolment at Sangklaburi is insufficient.
Number of Subjects
Up to 100 subjects will be enrolled to ensure a minimum of 59 subjects complete all study activities. This will allow for 40% subjects dropping out or being otherwise unevaluable. Up to 200 subjects may be screened to achieve the required number of evaluable subjects. A subject is considered evaluable at 72 hours from the commencement of artesunate treatment or once asexual parasites have been cleared from peripheral blood based on microscopy, whichever is longer.
Treatment
The antimalarial drug regimen being evaluated is: artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours; plus mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours; plus primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours.
Study Design and Methodology
This is an open-label, single-arm evaluation of AS-MQ combination for the treatment of uncomplicated P. falciparum malaria. Subjects will remain as in-patients until completion of antimalarial treatment and will then be followed up weekly to 42 days.
Study Endpoints
Primary Endpoint
- Parasite clearance rate as defined by the slope of the linear portion of the logarithm parasite clearance curve using microscopy to determine parasitemia
Secondary Endpoints
2.1. A description of the clinical and parasitological features of uncomplicated malaria in this setting (composite endpoint), including:
- Parasite clearance rate during the first 72 hours after artesunate administration as defined by the slope of the linear portion of the logarithm parasite clearance curve using qPCR to determine parasitemia
- Parasite reduction ratios at 24 and 48 hours assessed by microscopy and qPCR
- Time for parasite count to fall to 50%, 90%, 99% and 100% of initial parasite density
- Fever clearance time (i.e. the time taken for temperature to fall below 38.0˚C (tympanic method) or below 37.5˚C (axillary method) and remain there for at least 24 hours)
- 42-day PCR-adjusted treatment efficacy using World Health Organization classification of outcome.
2.2. Gametocyte carriage rates assessed in person weeks (up to 42 days) 2.3. Plasma levels of AS, DHA and MQ at selected time points 2.4. In vitro IC50, IC90, IC99 P. falciparum responses to a panel of antimalarial drugs, including dihydroartemisinin (DHA) and mefloquine.
2.5. Parasite molecular markers of drug resistance as determined by GWAS, SNP analysis and other genotyping methodologies 2.6. A detailed characterization of drug-resistant malaria using integrated endpoints above, including clinical, in vitro and molecular 2.7. Comparison of clinical and parasitological outcomes and in vitro and molecular features of parasites between harmonized sites in Kenya and Peru.
2.8. Identification of host factors that correlate with slow parasite clearance and other clinical outcomes 2.9. Creation of a well-characterised catalog of malaria parasites for future research
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| artesunate/mefloquine (AS/MQ) | Experimental | Drug: Artesunate/mefloquine (AS/MQ)The antimalarial drug regimen being evaluated is: artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours; plus mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours; plus primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Thai or non-Thai, otherwise healthy, male or female, aged from 5 years to 65 years inclusive
- Acute uncomplicated P. falciparum malaria monoinfection, confirmed by positive blood smear
- Asexual P. falciparum parasitaemia of 1,000 to 200,000 parasites/µL, confirmed on a thin or thick blood film
- Fever defined as ≥ 38.0°C tympanic temperature (or equivalent) or a history of fever within the last 24 hours
- Willingness to participate in the study as evidenced by written informed consent from the subject or parent/guardian (for children), and by assent (for children)
Key exclusion criteria (8 listed)
- Severe malaria as defined by WHO criteria (reference WHO 2012)
- Inability to eat or drink, inability to tolerate oral antimalarial medication, recent history of seizures (one or more in the previous 24 hours), altered level of consciousness, inability to sit or stand
- Mixed species asexual stage malaria infection as determined by microscopy
- Recent antimalarial treatment, defined as a clear history of any antimalarial medication taken within the previous 7 days; or a clear history of mefloquine within previous 4 weeks
- History of splenectomy
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 |
|---|---|---|
| Artesunate/mefloquine (AS/MQ)Also: Mequin* artesunate (AS) 4mg/kg by mouth once daily at 0, 24 and 48 hours * mefloquine (MQ) 15mg/kg by mouth once at 72 hours, and 10mg/kg once by mouth at 84-96 hours * primaquine (PQ) 0.5mg/kg single dose by mouth at 84-96 hours | Drug | artesunate/mefloquine (AS/MQ) |
Primary outcome
Parasite clearance rate
Time frame: one year
Parasite clearance rate as defined by the slope of the linear portion of the logarithm parasite clearance curve using microscopy to determine parasitemia
1 secondary outcome
Number of patients with prolonged parasite clearance times, adequate drug levels and positive molecular markers of parasite resistance.
Time frame: one year
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 Jan 2016.
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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.
Krisada Jongsakul, MD principal investigator
Armed Forces Research Institute of Medical Sciences, Thailand
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/mefloquine (AS/MQ) in people with Malaria, run by Armed Forces Research Institute of Medical Sciences, Thailand at 1 site in Thailand.
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 5 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 25 Jan 2016. 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 Thailand. 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?
Parasite clearance rate (time frame: one year). 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 Jan 2016; AzTrials last refreshed its copy on 4 Nov 2026.