Acute Uncomplicated Malaria With P.Vivax InfectionPhase 4NCT01662700
Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand
A Phase 4 study testing Artesunate and Chloroquine in people with Acute Uncomplicated Malaria With P.Vivax Infection, run by Mahidol University at 4 sites in Thailand.
Trial summary
In Thailand, the proportion of P.vivax infection has now been increasing and is equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Uncomplicated Malaria With P.Vivax Infection
- What is being tested?
- Artesunate and Chloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 4 sitesThailand
- Study dates
- Oct 2012to 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, aged from 18 years to 65 years old who can come to the study hospital for follow up in case of re-infection
- Acute uncomplicated malaria with P.vivax infection, confirmed by positive blood smear with asexual forms of P. vivax with parasitaemia > 1,000 parasites/microliters
- Fever defined as temperature > 37.5 degree celsius or a history of fever within the last 24 hours
- Written informed consent
- Willingness and ability of the patients/guardians to comply with the study protocol for the duration of the study
- Communicate with Thai language
Who cannot join
- Mixed infection with other plasmodium species
- For females: pregnancy, breast feeding
- History of allergy or known contraindication to chloroquine, artesunate or primaquine
- Any criteria of severe / complicated malaria (WHO 2010)
- Presence of febrile condition caused by disease other than malaria.
Trial locations and contacts
4 sites in 1 country.
Thailand4 sites, 4 recruiting
- Recruiting
Kraburi Hospital
Ranong
Thongchai Keeratihatayagorn, MD, +6681 8952244
Prakaykaew Charunwatthana, MD, +6681-844 9678, jib@tropmedres.ac
- Recruiting
Khunhan Hospital
Si Sa Ket, Changwat Si Sa Ket
Ratchadaporn Runchareon, MD, +6681-790-9275
Prakaykaew Charunwatthana, MD, +6681-844 9678, jib@tropmedres.ac
- Recruiting
Phusing Hospital
Si Sa Ket
Kitipumi Chutasmit, MD, +6687 9654139
Prakaykaew Charunwatthan, MD, +6681-844 9678, jib@tropmedres.ac
- Recruiting
Kap Choeng Hospital
Surin
Satawat Sinprasitkul, MD, +6681 7601087
Prakaykaew Charunwatthana, MD, +6681-844 9678, jib@tropmedres.ac
About this study
Official title: An Open Label Randomized Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand
In Thailand, the proportion of P.vivax infection has now been increasing and is equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.
Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as anti-relapse therapy. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported . The relapse rates at day 28 are about 50% without primaquine therapy and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).
Read more
Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai-Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.
The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.
Read the detailed description
Plasmodium vivax affects 70-80 million cases of malaria worldwide annually, is the major cause of human malaria in parts of Pacific region and South America. In Thailand, the proportion of P.vivax infection has increased and it is now equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.
Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as antirelapse therapy. However, chloroquine-resistant P.vivax (CRPv) has been emer-ging in different parts of the world. The first report of chloroquine resistant Plasmodium vivax was in 2 Australian soldiers returning from Papua New Guinea in Indonesia and is now spreading over Asia and the Pacific region. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported. Occasional failure of the standard primaquine therapy (15 mg daily for 14 days) to prevent relapse has been observed. However, primaquine resistance has not been confirmed. In Thailand, the relapse rates at day 28 are about 50% without primaquine therapy, and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).
A number of factors are reportedly associated with relapse, or the reappearance of P.vivax, including inadequate primaquine dosage, high parasitaemia at diagnosis, and short duration of symptoms prior to diagnosis, presence of gametocytes on admission, age, and gender. Because the radical cure of P.vivax hypnozoites requires 14 days of primaquine therapy, adherence to the drug regimen may greatly affect the prevention of relapse. Unfortunately, the effect of patient adherence on 14 day primaquine treatment, and its relation to preventing parasite reappearance, is not well-document.
Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai_Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.
The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.
- Being tested
- Artesunate, Chloroquine
- Keywords
- P. vivax infection, Artesunate, Chloroquine, Primaquine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArtesunateDrug
ChloroquineDrug
| Study group | Role | What they receive |
|---|---|---|
| AS2 | Experimental | Artesunate 2 mg/kg/day for 5 days Combine with
* Primaquine 15 mg is given daily for 14 days.
* Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients. Receives: Drug: Artesunate |
| Chloroquine | Active comparator | CH25: Chloroquine 25 mg/kg: 15 mg base/kg on the first days (D0), followed by 5 mg base/kg daily on the second and third day (day1-2) (total 25 mg base/ kg).
Combine with
* Primaquine 15 mg is given daily for 14 days.
* Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients. Receives: Drug: Chloroquine |
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 natural logarithm parasite clearance curve
Measured: 7 days
Relapse rate of P. vivax
Incidence of relapse in P.vivax infection
Measured: 3 months
Secondary outcomes (5)
Parasite clearance time
Parasite clearance time assessed by microscopy
Measured: 7 days
Parasite density time
Time of parasite count to fall to 50%, 90% and 99% of initial parasite density
Measured: 7 days
Fever clearance time
Fever clearance time (i.e. the time taken for temperature to fall below 37 degrees celsius and remain there for at least 24 hrs)
Measured: 7 days
Proportion of patients with gametocytemia
Proportion of patients with gametocytemia before, during and after treatment, assessed at admission, on day 3 stratified by presence of gametocytes at enrolment
Measured: 7 days
In vitro antimalarial drug susceptibility
IC0, IC90, IC99 of Plasmodium vivax responses to antimalarial drugs ( ex vivo)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Uncomplicated Malaria With P.Vivax InfectionStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- 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
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01662700
- Sponsor's protocol ID
- FTM1202
- Status last verified
- Jan 2013
- First submitted
- 8 Aug 2012
- Last updated
- 25 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Randomized Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand
- ClinicalTrials.gov ID
- NCT01662700
- Acronym / sponsor ID
- FTM1202
- Keywords
- P. vivax infection, Artesunate, Chloroquine, Primaquine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 10 Aug 2012 (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.
In Thailand, the proportion of P.vivax infection has now been increasing and is equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.
Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as anti-relapse therapy. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported . The relapse rates at day 28 are about 50% without primaquine therapy and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).
Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai-Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.
The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.
Detailed description
Plasmodium vivax affects 70-80 million cases of malaria worldwide annually, is the major cause of human malaria in parts of Pacific region and South America. In Thailand, the proportion of P.vivax infection has increased and it is now equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts.
Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as antirelapse therapy. However, chloroquine-resistant P.vivax (CRPv) has been emer-ging in different parts of the world. The first report of chloroquine resistant Plasmodium vivax was in 2 Australian soldiers returning from Papua New Guinea in Indonesia and is now spreading over Asia and the Pacific region. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported. Occasional failure of the standard primaquine therapy (15 mg daily for 14 days) to prevent relapse has been observed. However, primaquine resistance has not been confirmed. In Thailand, the relapse rates at day 28 are about 50% without primaquine therapy, and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days).
A number of factors are reportedly associated with relapse, or the reappearance of P.vivax, including inadequate primaquine dosage, high parasitaemia at diagnosis, and short duration of symptoms prior to diagnosis, presence of gametocytes on admission, age, and gender. Because the radical cure of P.vivax hypnozoites requires 14 days of primaquine therapy, adherence to the drug regimen may greatly affect the prevention of relapse. Unfortunately, the effect of patient adherence on 14 day primaquine treatment, and its relation to preventing parasite reappearance, is not well-document.
Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai_Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand.
The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AS2 | Experimental | Drug: ArtesunateArtesunate 2 mg/kg/day for 5 days Combine with * Primaquine 15 mg is given daily for 14 days. * Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients. |
| Chloroquine | Active comparator | Drug: ChloroquineCH25: Chloroquine 25 mg/kg: 15 mg base/kg on the first days (D0), followed by 5 mg base/kg daily on the second and third day (day1-2) (total 25 mg base/ kg). Combine with * Primaquine 15 mg is given daily for 14 days. * Or primaquine 45 mg is given once a week for 8 weeks in G6PD deficiency patients. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, aged from 18 years to 65 years old who can come to the study hospital for follow up in case of re-infection
- Acute uncomplicated malaria with P.vivax infection, confirmed by positive blood smear with asexual forms of P. vivax with parasitaemia > 1,000 parasites/microliters
- Fever defined as temperature > 37.5 degree celsius or a history of fever within the last 24 hours
- Written informed consent
- Willingness and ability of the patients/guardians to comply with the study protocol for the duration of the study
Key exclusion criteria (5 listed)
- Mixed infection with other plasmodium species
- For females: pregnancy, breast feeding
- History of allergy or known contraindication to chloroquine, artesunate or primaquine
- Any criteria of severe / complicated malaria (WHO 2010)
- Presence of febrile condition caused by disease other than malaria.
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 | Drug | AS2 |
| Chloroquine | Drug | Chloroquine |
Primary outcome
Parasite Clearance Rate
Time frame: 7 days
Parasite clearance rate as defined by the slope of the linear portion of the natural logarithm parasite clearance curve
Relapse rate of P. vivax
Time frame: 3 months
Incidence of relapse in P.vivax infection
5 secondary outcomes
Parasite clearance time
Time frame: 7 days
Parasite density time
Time frame: 7 days
Fever clearance time
Time frame: 7 days
Proportion of patients with gametocytemia
Time frame: 7 days
In vitro antimalarial drug susceptibility
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2013.
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.
4 sites 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 and Chloroquine in people with Acute Uncomplicated Malaria With P.Vivax Infection, run by Mahidol University at 4 sites 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 6 inclusion and 5 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 25 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parasite Clearance Rate (time frame: 7 days). The study lists 2 primary outcomes in all. 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 2013.