MalariaPhase 3NCT00158561
Chlorproguanil/Dapsone Compared With Chloroquine and SP for Vivax Malaria
A Phase 3 study testing sulfadoxine-pyrimethamine and chlorproguanil-dapsone in people with Malaria and Vivax Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Pakistan.
Trial summary
To determine whether two cheap antifolates (chlorproguanil-dapsone and sulfadoxine-pyrimethamine) which work against falciparum malaria in this region are sufficiently effective against vivax malaria to be deployed in areas where diagnosis is poor and the burden of malaria is high, a randomised controlled trial of the… Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Malaria, Vivax Malaria
- What is being tested?
- sulfadoxine-pyrimethamine and chlorproguanil-dapsone
- How many people
- 750 participants
- Where
- 1 sitePakistan
- Study dates
- Feb 2004to Mar 2006
- Phase
- Phase 3
- 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Presentation at BHU or clinic with probable clinical malaria.
- Infection with P. vivax, confirmed by microscopy.
- Age 3 years or older (no restriction on upper age limit).
- Written or witnessed verbal consent obtained from the patient or the patients parent or guardian.
- Married women of child bearing age confirmed to be non-pregnant at outset and willing to remain thus for the duration of the study.
- Willingness to comply with the requirements of the protocol and particularly to provide venous and thumb prick blood samples.
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- Available for follow up for the duration of the study and not less than 6 months.
- Willingness to report to the BHU or clinic if they feel unwell in the 6 months following completion (i.e. 7 months from enrolment date). NB these patients will only be those recruited up to 7 months before the end of the study period.
- Availability of G6PD status by willingness to be tested at admission.
Who cannot join
- General condition requiring hospital admission.
- Evidence of any concomitant infection likely to mask treatment response at the time of presentation.
- Presence of any other underlying disease that compromises the diagnosis and the evaluation of the response to the study medication.
- History of allergy to sulphonamides, dapsone or chloroquine or hypersensitivity to biguanides (eg proguanil, chlorproguanil) sulphones (eg frusemide, thiazides, acetazolamide, and sulphonylureas) or any other tablet contents.
- Known methaemoglobin reductase deficiency and haemoglobin M.
- Treatment within the past twenty-eight days with sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), mefloquine-sulfadoxine-pyrimethamine (Fansimef); 21-days with mefloquine, or 7-days with amodiaquine, chloroquine, halofantrine, quinine (full course), primaquine, atovaquone - proguanil, artemisinin derivatives, co-artemether, trimethoprim, chloramphenicol, erythromycin, tetracycline or clindamycin.
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- Visible jaundice.
- Use of an investigational drug within 30 days or 5 half-lives whichever is the longer.
- Severe anaemia (Hb<7 g/dl).
- Other species of malaria seen.
- Pregnancy, assessed by pregnancy test in all married women of child-bearing age (age over 14 and under 50).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Three Arm Trial of the Efficacy and Safety of Chlorproguanil / Dapsone (Lapdap) Compared With Chloroquine and Sulfadoxine / Pyrimethamine for the Treatment of Vivax Malaria in Pakistan and Afghanistan
To determine whether two cheap antifolates (chlorproguanil-dapsone and sulfadoxine-pyrimethamine) which work against falciparum malaria in this region are sufficiently effective against vivax malaria to be deployed in areas where diagnosis is poor and the burden of malaria is high, a randomised controlled trial of the three drugs is being undertaken comparing their efficacy in treating malaria.
Read the detailed description
Objectives:
Primary:
To evaluate the comparative efficacy of chlorproguanil / dapsone with sulfadoxine-pyrimethamine for the treatment of vivax malaria in Pakistan and eastern Afghanistan.
Secondary:
- To compare the efficacy of chlorproguanil-dapsone and sulfadoxine-pyrimethamine with chloroquine
- To evaluate the safety profile of chlorproguanil / dapsone in south Asians from this region when used for the treatment of vivax malaria.
- To evaluate the effect of chlorproguanil / dapsone on gametocyte clearance rates.
- To evaluate the effect of chlorproguanil / dapsone on subsequent relapse due to vivax malaria.
Study Population:
750 P.vivax positive individuals recruited from the Malaria Reference Centre in Jalalabad, Afghanistan and at health facilities in Afghan refugee camps in North West Frontier Province (NWFP), Pakistan supervised by HealthNet International
Efficacy Parameters :
Primary Efficacy Variable:
- Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation. Slides will be double read.
Secondary Efficacy Variables
- Day 28 slide clearance rate defined as the number of treated patients with clearance of parasitaemia within 14 days of starting treatment, without subsequent recrudescence up to day 28.
- Day 14 clinical failure rate (presence of symptoms of malaria in the presence of parasitaemia).
- Day 28 clinical failure rate.
- Adverse events.
- Haemoglobin level increased by at least 1g/dl by day 14.
- Clearance of gametocytaemia by day 3, 7, and 14.
- Number of subsequent malaria episodes in next 6 months. It is assumed that the population of each treatment arm is equally likely to be re-infected in this time scale. Therefore any measurable difference in number of subsequent episodes between treatment arms will be due to a relapse.
- In G6PD deficient patients the change in mean haemoglobin.
Safety Parameters:
Adverse events and laboratory findings will be monitored in all patients. Regular haemoglobin to identify haemolysis.
Study design:
Recruitment and administration:
Recruitment and administration of all treatments will be directly observed by the trial coordinator and trial pharmacist, and/or health unit clinician.
Dosing Schedules:
Chlorproguanil-dapsone (Lapdap): (target doses 2.0 and 2.5 mg/kg respectively) daily for 3 days .
Sulfadoxine - pyrimethamine (SP): (target doses 1.25 and 25.0 mg/kg respectively) once only.
Chloroquine (CQ): (target dose 25mg/kg ) daily for 3 days.
Follow up:
Patients will return to the clinic on days 0, 1, 2, 3, 7, 14, 21 and 28 for supervised dosing, thick and thin smears, blood spot filter papers, update of clinical record forms, determination of haemoglobin, full blood cell counts, liver function tests, determination of adverse events and concomitant medication details, as appropriate.
- Conditions
- Malaria, Vivax Malaria
- Being tested
- sulfadoxine-pyrimethamine and chlorproguanil-dapsone
- Keywords
- vivax, treatment, Asia
- Medical subject headings
- Malaria, Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sulfadoxine-pyrimethamine and chlorproguanil-dapsoneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation.
Secondary outcomes (8)
Day 28 slide clearance rate defined as the number of treated patients with clearance of parasitaemia within 14 days of starting treatment, without subsequent recrudescence up to day 28.
Day 14 clinical failure rate (presence of symptoms of malaria in the presence of parasitaemia).
Day 28 clinical failure rate.
Adverse events.
Haemoglobin level increased by at least 1g/dl by day 14.
Clearance of gametocytaemia by day 3, 7, and 14.
Number of subsequent malaria episodes in next 6 months. It is assumed that the population of each treatment arm is equally likely to be re-infected in this time scale. Therefore any measurable difference in number of subsequent episodes between treatment
In G6PD deficient patients the change in mean haemoglobin.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startFeb 2004
- Study completionMar 2006
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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 750 participants
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- HealthNet TPO
- Responsible party
- Principal investigator, Brian Greenwood, London School of Hygiene and Tropical Medicine
- Investigators
- Christopher Whitty, FRCP, Principal investigator, London School of Hygiene and Tropical MedicineMark Rowland, PhD, Study director, London School of Hygiene and Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00158561
- Sponsor's protocol ID
- ITDCKD45
- Status last verified
- Jan 2017
- First submitted
- 9 Sep 2005
- Last updated
- 12 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Leslie T, Mayan MI, Hasan MA, Safi MH, Klinkenberg E, Whitty CJ, Rowland M. Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial. JAMA. 2007 May 23;297(20):2201-9. doi: 10.1001/jama.297.20.2201.
PubMed 17519409
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Three Arm Trial of the Efficacy and Safety of Chlorproguanil / Dapsone (Lapdap) Compared With Chloroquine and Sulfadoxine / Pyrimethamine for the Treatment of Vivax Malaria in Pakistan and Afghanistan
- ClinicalTrials.gov ID
- NCT00158561
- Acronym / sponsor ID
- ITDCKD45
- Conditions
- Malaria, Vivax Malaria
- Keywords
- vivax, treatment, Asia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 750 participants
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- HealthNet TPO
- Study start
- Feb 2004
- Study completion
- Mar 2006 (actual)
- First posted
- 12 Sep 2005 (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.
To determine whether two cheap antifolates (chlorproguanil-dapsone and sulfadoxine-pyrimethamine) which work against falciparum malaria in this region are sufficiently effective against vivax malaria to be deployed in areas where diagnosis is poor and the burden of malaria is high, a randomised controlled trial of the three drugs is being undertaken comparing their efficacy in treating malaria.
Detailed description
Objectives:
Primary:
To evaluate the comparative efficacy of chlorproguanil / dapsone with sulfadoxine-pyrimethamine for the treatment of vivax malaria in Pakistan and eastern Afghanistan.
Secondary:
- To compare the efficacy of chlorproguanil-dapsone and sulfadoxine-pyrimethamine with chloroquine
- To evaluate the safety profile of chlorproguanil / dapsone in south Asians from this region when used for the treatment of vivax malaria.
- To evaluate the effect of chlorproguanil / dapsone on gametocyte clearance rates.
- To evaluate the effect of chlorproguanil / dapsone on subsequent relapse due to vivax malaria.
Study Population:
750 P.vivax positive individuals recruited from the Malaria Reference Centre in Jalalabad, Afghanistan and at health facilities in Afghan refugee camps in North West Frontier Province (NWFP), Pakistan supervised by HealthNet International
Efficacy Parameters :
Primary Efficacy Variable:
- Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation. Slides will be double read.
Secondary Efficacy Variables
- Day 28 slide clearance rate defined as the number of treated patients with clearance of parasitaemia within 14 days of starting treatment, without subsequent recrudescence up to day 28.
- Day 14 clinical failure rate (presence of symptoms of malaria in the presence of parasitaemia).
- Day 28 clinical failure rate.
- Adverse events.
- Haemoglobin level increased by at least 1g/dl by day 14.
- Clearance of gametocytaemia by day 3, 7, and 14.
- Number of subsequent malaria episodes in next 6 months. It is assumed that the population of each treatment arm is equally likely to be re-infected in this time scale. Therefore any measurable difference in number of subsequent episodes between treatment arms will be due to a relapse.
- In G6PD deficient patients the change in mean haemoglobin.
Safety Parameters:
Adverse events and laboratory findings will be monitored in all patients. Regular haemoglobin to identify haemolysis.
Study design:
Recruitment and administration:
Recruitment and administration of all treatments will be directly observed by the trial coordinator and trial pharmacist, and/or health unit clinician.
Dosing Schedules:
Chlorproguanil-dapsone (Lapdap): (target doses 2.0 and 2.5 mg/kg respectively) daily for 3 days .
Sulfadoxine - pyrimethamine (SP): (target doses 1.25 and 25.0 mg/kg respectively) once only.
Chloroquine (CQ): (target dose 25mg/kg ) daily for 3 days.
Follow up:
Patients will return to the clinic on days 0, 1, 2, 3, 7, 14, 21 and 28 for supervised dosing, thick and thin smears, blood spot filter papers, update of clinical record forms, determination of haemoglobin, full blood cell counts, liver function tests, determination of adverse events and concomitant medication details, as appropriate.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Presentation at BHU or clinic with probable clinical malaria.
- Infection with P. vivax, confirmed by microscopy.
- Age 3 years or older (no restriction on upper age limit).
- Written or witnessed verbal consent obtained from the patient or the patients parent or guardian.
- Married women of child bearing age confirmed to be non-pregnant at outset and willing to remain thus for the duration of the study.
Key exclusion criteria (11 listed)
- General condition requiring hospital admission.
- Evidence of any concomitant infection likely to mask treatment response at the time of presentation.
- Presence of any other underlying disease that compromises the diagnosis and the evaluation of the response to the study medication.
- History of allergy to sulphonamides, dapsone or chloroquine or hypersensitivity to biguanides (eg proguanil, chlorproguanil) sulphones (eg frusemide, thiazides, acetazolamide, and sulphonylureas) or any other tablet contents.
- Known methaemoglobin reductase deficiency and haemoglobin M.
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 |
|---|---|---|
| sulfadoxine-pyrimethamine and chlorproguanil-dapsone | Drug | – |
Primary outcome
Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation.
8 secondary outcomes
Day 28 slide clearance rate defined as the number of treated patients with clearance of parasitaemia within 14 days of starting treatment, without subsequent recrudescence up to day 28.
Day 14 clinical failure rate (presence of symptoms of malaria in the presence of parasitaemia).
Day 28 clinical failure rate.
Adverse events.
Haemoglobin level increased by at least 1g/dl by day 14.
Clearance of gametocytaemia by day 3, 7, and 14.
Number of subsequent malaria episodes in next 6 months. It is assumed that the population of each treatment arm is equally likely to be re-infected in this time scale. Therefore any measurable difference in number of subsequent episodes between treatment
In G6PD deficient patients the change in mean haemoglobin.
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 12 Jan 2017.
- Results publication: PubMed 17519409Leslie T, Mayan MI, Hasan MA, Safi MH, Klinkenberg E, Whitty CJ, Rowland M. Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial. JAMA. 2007 May 23;297(20):2201-9. doi: 10.1001/jama.297.20.2201.
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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.
Christopher Whitty, FRCP principal investigator
London School of Hygiene and Tropical Medicine
Mark Rowland, PhD study director
London School of Hygiene and Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sulfadoxine-pyrimethamine and chlorproguanil-dapsone in people with Malaria and Vivax Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Pakistan.
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 9 inclusion and 11 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 12 Jan 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 Pakistan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation.. 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 NCT00158561, 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 12 Jan 2017.