MalariaPhase 2NCT01165372
Study of Malaria Treatment at Phuoc Long Hospital, Binh Phuoc Province, Vietnam
A Phase 2 study testing Artesunate or dihydroartemisinin-piperaquine in people with Malaria, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
Trial summary
Background: There are worrying signs from Western Cambodia that parasitological responses to artesunate containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Delayed parasite clearance and unusually high failure rates with artesunate-mefloquine have been reported. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Malaria
- What is being tested?
- Artesunate or dihydroartemisinin-piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 1 siteVietnam
- Study dates
- Aug 2010to May 2011
- Phase
- Phase 2
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- male and aged > 10 years OR;
- female patients > 10 and <12 years old, provided they have not reached menarche
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 10,000 - 100,000/µl asexual forms;
- presence of axillary or tympanic 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/assent.
Who cannot join
- presence of general danger signs or severe falciparum malaria according to the definitions of WHO;
- 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, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
- 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;
- treatment with antimalarial drugs in the previous 48 hours;
- history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);
- splenectomy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Investigation of In-vivo Susceptibility of P. Falciparum to Artesunate in Phuoc Long Hospital, Binh Phuoc Province, Vietnam
Background: There are worrying signs from Western Cambodia that parasitological responses to artesunate containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Delayed parasite clearance and unusually high failure rates with artesunate-mefloquine have been reported. These antimalarials are central to current treatment strategies and spread of significant resistance outside this area would be a global disaster. Radical containment measures are needed. In this context there is an urgent need to proceed quickly to investigate whether there is any evidence of resistance to artemisinin derivatives in Vietnam.
Objective: The primary objective is to assess the slope of the decline in the log parasitemia-time curve in patients treated with artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily, and to compare the results of this study to the pharmacokinetic results and to the recent data from patients in Cambodia and Thailand treated with equivalent therapies.
Methods: The trial will be conducted in Phuoc Long Hospital, Binh Phuoc Province, Vietnam. The participants will be febrile patients (aged > 10 years) with slide confirmed uncomplicated P. falciparum infection. Patients will be treated with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily for 3 days. Patients on artesunate therapy arms will then receive 3 days of treatment with dihydroartemisinin-piperaquine with dosages according to the national guidelines. Clinical and parasitological parameters will be monitored over a 42-day follow-up period. The pharmacokinetic characteristics of artesunate and dihydroartemisinin will be assessed by using a population pharmacokinetic modeling.
Read the detailed description
This surveillance study is a three-arm prospective evaluation of the efficacy of artesunate and dihydroartemisinin-piperaquine in acute uncomplicated falciparum malaria. This will be an evaluation of the slope of the decline in the log parasitemia-time curve, parasite clearance times in patients randomized to one of two different doses of oral artesunate or dihydroartemisinin-piperaquine. People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily according to weight for 3 days. The artesunate arms will immediately follow with dihydroartemisinin-piperaquine therapy for 3 days (study days 3 - 6) at the dose defined by national guidelines. Patients on all three arms will be monitored for 42 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. PCR analysis will be used to distinguish between true recrudescence due to treatment failure and reinfection.
- Conditions
- Malaria
- Being tested
- Artesunate or dihydroartemisinin-piperaquine
- Keywords
- Malaria, Drug resistance
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artesunate or dihydroartemisinin-piperaquineDrug
artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily
| Study group | Role | What they receive |
|---|---|---|
| Artesunate 2mg | Experimental | People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 2mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days. Receives: Drug: Artesunate or dihydroartemisinin-piperaquine |
| Artesunate 4mg | Experimental | People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 4mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days. Receives: Drug: Artesunate or dihydroartemisinin-piperaquine |
| DHA-piperaquine | Experimental | People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with dihydroartemisinin-piperaquine once daily according to weight for 3 days. Receives: Drug: Artesunate or dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Slope of the decline in the log parasitemia-time curve relative to historical data
Measured: 03 days
Secondary outcomes (8)
Clearance rate assessed from the fitted slope of the log-linear parasite curves
Measured: 72 hours
Proportion of patients who have a parasite clearance time >72 hours after initiation of each treatment
Measured: 72 hours
Parasitological efficacy of the three treatment arms
Measured: Over 72 hours and during follow-up treatment over a total follow-up period of 42 days
Relative proportion of patients treated with artesunate 2mg/kg/day versus artesunate 4mg/kg/day versus dihydroartemisinin-piperaquine once daily
Patients who result as early treatment failures, late clinical failures, late parasitological failures or adequate clinical and parasitological response as indicators of efficacy
Measured: 03 days
Recrudescence and new infection rate defined by polymerase chain reaction (PCR) analysis between treatment arms
Measured: 42 days
Number of adverse events in each treatment arm
Measured: After initiation and during follow-up treatment over a total follow-up period of 42 days.
Assess the pharmacokinetic characteristics of artesunate and dihydroartemisinin-piperaquine by using population pharmacokinetic modeling
Measured: 03 days and upon relapse
Characterize different genetic patterns from different resistant strains
Measured: 03 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study startAug 2010
- Primary completionMay 2011
- Study completionMay 2011
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Clinical Research Unit, Vietnam
- Sponsor type
- University, hospital or other
- Collaborators
- World Health Organization
- Responsible party
- Sponsor
- Investigators
- Hien T Tran, MD, PhD, Principal investigator, Oxford University Clinical Research Unit, Vietnam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165372
- Sponsor's protocol ID
- 02MA
- Status last verified
- Sep 2011
- First submitted
- 15 Jul 2010
- Last updated
- 15 Sep 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Investigation of In-vivo Susceptibility of P. Falciparum to Artesunate in Phuoc Long Hospital, Binh Phuoc Province, Vietnam
- ClinicalTrials.gov ID
- NCT01165372
- Acronym / sponsor ID
- 02MA
- Conditions
- Malaria
- Keywords
- Malaria, Drug resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Oxford University Clinical Research Unit, VietnamUniversity, hospital or other
- Collaborators
- World Health Organization
- Study start
- Aug 2010
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 19 Jul 2010 (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: There are worrying signs from Western Cambodia that parasitological responses to artesunate containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Delayed parasite clearance and unusually high failure rates with artesunate-mefloquine have been reported. These antimalarials are central to current treatment strategies and spread of significant resistance outside this area would be a global disaster. Radical containment measures are needed. In this context there is an urgent need to proceed quickly to investigate whether there is any evidence of resistance to artemisinin derivatives in Vietnam.
Objective: The primary objective is to assess the slope of the decline in the log parasitemia-time curve in patients treated with artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily, and to compare the results of this study to the pharmacokinetic results and to the recent data from patients in Cambodia and Thailand treated with equivalent therapies.
Methods: The trial will be conducted in Phuoc Long Hospital, Binh Phuoc Province, Vietnam. The participants will be febrile patients (aged > 10 years) with slide confirmed uncomplicated P. falciparum infection. Patients will be treated with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily for 3 days. Patients on artesunate therapy arms will then receive 3 days of treatment with dihydroartemisinin-piperaquine with dosages according to the national guidelines. Clinical and parasitological parameters will be monitored over a 42-day follow-up period. The pharmacokinetic characteristics of artesunate and dihydroartemisinin will be assessed by using a population pharmacokinetic modeling.
Detailed description
This surveillance study is a three-arm prospective evaluation of the efficacy of artesunate and dihydroartemisinin-piperaquine in acute uncomplicated falciparum malaria. This will be an evaluation of the slope of the decline in the log parasitemia-time curve, parasite clearance times in patients randomized to one of two different doses of oral artesunate or dihydroartemisinin-piperaquine. People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with either artesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily according to weight for 3 days. The artesunate arms will immediately follow with dihydroartemisinin-piperaquine therapy for 3 days (study days 3 - 6) at the dose defined by national guidelines. Patients on all three arms will be monitored for 42 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. PCR analysis will be used to distinguish between true recrudescence due to treatment failure and reinfection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Artesunate 2mg | Experimental | Drug: Artesunate or dihydroartemisinin-piperaquinePeople with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 2mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days. |
| Artesunate 4mg | Experimental | Drug: Artesunate or dihydroartemisinin-piperaquinePeople with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with artesunate 4mg/kg/day for 3 days and followed by DHA-PPQ treatment at doses according to National guidelines for 3 days. |
| DHA-piperaquine | Experimental | Drug: Artesunate or dihydroartemisinin-piperaquinePeople with uncomplicated malaria who meet the study inclusion criteria will be enrolled, screened, randomized and treated on site with dihydroartemisinin-piperaquine once daily according to weight for 3 days. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- male and aged > 10 years OR;
- female patients > 10 and <12 years old, provided they have not reached menarche
- mono-infection with P. falciparum detected by microscopy;
- parasitaemia of 10,000 - 100,000/µl asexual forms;
- presence of axillary or tympanic temperature ≥ 37.5 °C or history of fever during the past 24 h;
Key exclusion criteria (8 listed)
- presence of general danger signs or severe falciparum malaria according to the definitions of WHO;
- 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, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
- 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 |
|---|---|---|
| Artesunate or dihydroartemisinin-piperaquineartesunate 2mg/kg/day, artesunate 4mg/kg/day or dihydroartemisinin-piperaquine once daily | Drug | Artesunate 2mg, Artesunate 4mg, DHA-piperaquine |
Primary outcome
Slope of the decline in the log parasitemia-time curve relative to historical data
Time frame: 03 days
8 secondary outcomes
Clearance rate assessed from the fitted slope of the log-linear parasite curves
Time frame: 72 hours
Proportion of patients who have a parasite clearance time >72 hours after initiation of each treatment
Time frame: 72 hours
Parasitological efficacy of the three treatment arms
Time frame: Over 72 hours and during follow-up treatment over a total follow-up period of 42 days
Relative proportion of patients treated with artesunate 2mg/kg/day versus artesunate 4mg/kg/day versus dihydroartemisinin-piperaquine once daily
Time frame: 03 days
Recrudescence and new infection rate defined by polymerase chain reaction (PCR) analysis between treatment arms
Time frame: 42 days
Number of adverse events in each treatment arm
Time frame: After initiation and during follow-up treatment over a total follow-up period of 42 days.
Assess the pharmacokinetic characteristics of artesunate and dihydroartemisinin-piperaquine by using population pharmacokinetic modeling
Time frame: 03 days and upon relapse
Characterize different genetic patterns from different resistant strains
Time frame: 03 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 15 Sep 2011.
- Related InfoLink provided by the sponsor.
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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.
Hien T Tran, MD, PhD principal investigator
Oxford University Clinical Research Unit, Vietnam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Artesunate or dihydroartemisinin-piperaquine in people with Malaria, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
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 8 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 15 Sep 2011. 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 Vietnam. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Slope of the decline in the log parasitemia-time curve relative to historical data (time frame: 03 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 15 Sep 2011.