MalariaPhase 4ASAPNCT02297477
The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia
A Phase 4 study testing atovaquone-proguanil and artesunate-atovaquone-proguanil in people with Malaria, run by Armed Forces Research Institute of Medical Sciences, Thailand at 1 site in Cambodia.
Trial summary
This is a two-arm, randomized, open label Treatment Study evaluating the therapeutic efficacy, safety, tolerability and pharmacokinetics of a three-day course of Atovaquone-Proguanil (AP) or a three-day course of Atovaquone-Proguanil combined with 3 days of Artesunate (ASAP) in patients with uncomplicated Plasmodium… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Malaria
- What is being tested?
- atovaquone-proguanil and artesunate-atovaquone-proguanil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 1 siteCambodia
- Study dates
- Dec 2014to Dec 2021
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
- Baseline asexual parasite density between 100-200,000 parasites/microL
- Able to provide informed consent
- Available and agree to follow-up for anticipated study duration including 3 day treatment course at the Medical Treatment Facility, and weekly follow-up for the 42-day period.
Who cannot join
- Allergic reaction or medical contraindication to atovaquone, proguanil, artesunate or primaquine, to include a calculated serum creatinine clearance estimate of less than 30mL/min
- Significant acute comorbidity requiring urgent medical intervention
- Signs/symptoms and parasitological confirmation of severe malaria
- Use of any anti-malarial within the past 7 days, or atovaquone-proguanil in the past 30 days
- Use of the following concomitant medications within 7 days, which may cause or be volunteers to significant drug-drug interactions with study drug - tetracycline, metoclopramide, rifampin, rifabutin, zidovudine or etoposide.
- Pregnant or lactating female, or female of childbearing age, up to 50 years of age, who does not agree to use an acceptable form of contraception during the study
- Judged by the investigator to be otherwise unsuitable for study participation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Therapeutic Efficacy of Atovaquone-proguanil and Artesunate-atovaquone-proguanil for the Treatment of Uncomplicated P. Falciparum Malaria in Areas of Multidrug Resistance in Cambodia.
This is a two-arm, randomized, open label Treatment Study evaluating the therapeutic efficacy, safety, tolerability and pharmacokinetics of a three-day course of Atovaquone-Proguanil (AP) or a three-day course of Atovaquone-Proguanil combined with 3 days of Artesunate (ASAP) in patients with uncomplicated Plasmodium falciparum malaria at selected sites in Cambodia. Atovaquone-proguanil, soon to adopted as a first line antimalarial agent by the National Malaria Control Program (CNM) in Cambodia in provinces with confirmed multidrug resistance, will be given with or without artesunate (AS) as a directly observed, standard three-day fixed dose combination treatment to all volunteers enrolled. The efficacy and safety of both drug combination as well as evidence for in vivo and in vitro resistance to their components will be monitored during the treatment period. All volunteers will receive a single dose of 15mg of primaquine as recommended by WHO with the first dose of AP or ASAP to block the transmission of malaria to mosquitoes. Resistance to AP and ASAP will be assessed by a combination of clinical, pharmacologic, and parasitological parameters including genomic signatures of selection during careful weekly follow-up visits for 6 weeks. Investigators will also be able to evaluate the effects of primaquine on the sexual stages of malaria (gametocytes).
- Conditions
- Malaria
- Being tested
- atovaquone-proguanil, artesunate-atovaquone-proguanil
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atovaquone-proguanilDrug
A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively)
artesunate-atovaquone-proguanilDrug
A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg daily respectively) in addition to 4 tablets containing 50mg artesunate (200mg daily)
| Study group | Role | What they receive |
|---|---|---|
| atovaquone-proguanil (AP) | Active comparator | A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) for treatment of uncomplicated P. falciparum malaria. Receives: Drug: atovaquone-proguanil |
| artesunate-atovaquone-proguanil (ASAP) | Active comparator | A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) plus 3 days of artesunate (200mg per day) for treatment of uncomplicated P. falciparum malaria. Receives: Drug: artesunate-atovaquone-proguanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy at 42 days (with 95% confidence intervals) for AP with and without artesunate for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Measured: 6 weeks
Secondary outcomes (3)
Efficacy at 28 days (with 95% confidence intervals) for atovaquone-proguanil and artesunate-atovaquone-proguanil for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Measured: 4 weeks
Rates of sexual stage infections at days 1, 4, week 1 and week 2 based on a combined endpoint of light microscopy and PCR analysis for detection of gametocyte maturity.
Measured: 2 weeks
Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2015
- Study completionDec 2021 (estimated)
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- Armed Forces Research Institute of Medical Sciences, Thailand
- Sponsor type
- Other government
- Collaborators
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Naval Medical Research Center, Asia (NMRC-A)
- Responsible party
- Sponsor
- Investigators
- Lek Dysoley, MD, Principal investigator, National Center for Parasitology, Entomology and Malaria ControlMariusz Wojnarski, MD, Principal investigator, Armed Forces Research Institute of Medical Sciences (AFRIMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02297477
- Sponsor's protocol ID
- WR2115
- Acronym
- ASAP
- Status last verified
- Mar 2021
- First submitted
- 18 Oct 2014
- Last updated
- 2 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Efficacy of Atovaquone-proguanil and Artesunate-atovaquone-proguanil for the Treatment of Uncomplicated P. Falciparum Malaria in Areas of Multidrug Resistance in Cambodia.
- ClinicalTrials.gov ID
- NCT02297477
- Acronym / sponsor ID
- ASAP / WR2115
- Conditions
- Malaria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 205 participants (actual)
- Lead sponsor
- Armed Forces Research Institute of Medical Sciences, ThailandOther government
- Collaborators
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Naval Medical Research Center, Asia (NMRC-A)
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2021 (estimated)
- First posted
- 21 Nov 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.
This is a two-arm, randomized, open label Treatment Study evaluating the therapeutic efficacy, safety, tolerability and pharmacokinetics of a three-day course of Atovaquone-Proguanil (AP) or a three-day course of Atovaquone-Proguanil combined with 3 days of Artesunate (ASAP) in patients with uncomplicated Plasmodium falciparum malaria at selected sites in Cambodia. Atovaquone-proguanil, soon to adopted as a first line antimalarial agent by the National Malaria Control Program (CNM) in Cambodia in provinces with confirmed multidrug resistance, will be given with or without artesunate (AS) as a directly observed, standard three-day fixed dose combination treatment to all volunteers enrolled. The efficacy and safety of both drug combination as well as evidence for in vivo and in vitro resistance to their components will be monitored during the treatment period. All volunteers will receive a single dose of 15mg of primaquine as recommended by WHO with the first dose of AP or ASAP to block the transmission of malaria to mosquitoes. Resistance to AP and ASAP will be assessed by a combination of clinical, pharmacologic, and parasitological parameters including genomic signatures of selection during careful weekly follow-up visits for 6 weeks. Investigators will also be able to evaluate the effects of primaquine on the sexual stages of malaria (gametocytes).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| atovaquone-proguanil (AP) | Active comparator | Drug: atovaquone-proguanilA standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) for treatment of uncomplicated P. falciparum malaria. |
| artesunate-atovaquone-proguanil (ASAP) | Active comparator | Drug: artesunate-atovaquone-proguanilA standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) plus 3 days of artesunate (200mg per day) for treatment of uncomplicated P. falciparum malaria. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
- Baseline asexual parasite density between 100-200,000 parasites/microL
- Able to provide informed consent
- Available and agree to follow-up for anticipated study duration including 3 day treatment course at the Medical Treatment Facility, and weekly follow-up for the 42-day period.
Key exclusion criteria (7 listed)
- Allergic reaction or medical contraindication to atovaquone, proguanil, artesunate or primaquine, to include a calculated serum creatinine clearance estimate of less than 30mL/min
- Significant acute comorbidity requiring urgent medical intervention
- Signs/symptoms and parasitological confirmation of severe malaria
- Use of any anti-malarial within the past 7 days, or atovaquone-proguanil in the past 30 days
- Use of the following concomitant medications within 7 days, which may cause or be volunteers to significant drug-drug interactions with study drug - tetracycline, metoclopramide, rifampin, rifabutin, zidovudine or etoposide.
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 |
|---|---|---|
| atovaquone-proguanilA daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively) | Drug | atovaquone-proguanil (AP) |
| artesunate-atovaquone-proguanilA daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg daily respectively) in addition to 4 tablets containing 50mg artesunate (200mg daily) | Drug | artesunate-atovaquone-proguanil (ASAP) |
Primary outcome
Efficacy at 42 days (with 95% confidence intervals) for AP with and without artesunate for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Time frame: 6 weeks
3 secondary outcomes
Efficacy at 28 days (with 95% confidence intervals) for atovaquone-proguanil and artesunate-atovaquone-proguanil for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Time frame: 4 weeks
Rates of sexual stage infections at days 1, 4, week 1 and week 2 based on a combined endpoint of light microscopy and PCR analysis for detection of gametocyte maturity.
Time frame: 2 weeks
Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group.
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
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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.
Lek Dysoley, MD principal investigator
National Center for Parasitology, Entomology and Malaria Control
Mariusz Wojnarski, MD principal investigator
Armed Forces Research Institute of Medical Sciences (AFRIMS)
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 atovaquone-proguanil and artesunate-atovaquone-proguanil in people with Malaria, run by Armed Forces Research Institute of Medical Sciences, Thailand at 1 site in Cambodia.
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 4 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: status not confirmed, as of the sponsor's last update on 2 Mar 2021. 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 Cambodia. 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?
Results are not available in the source record.
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?
Efficacy at 42 days (with 95% confidence intervals) for AP with and without artesunate for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy. (time frame: 6 weeks). 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 2 Mar 2021.