Chlorproguanil/Dapsone Compared With Chloroquine and SP for Vivax Malaria

January 11, 2017 updated by: Brian Greenwood, London School of Hygiene and Tropical Medicine

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment

750

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
      • Peshawar, Pakistan
        • HealthNet International

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Presentation at BHU or clinic with probable clinical malaria.
  2. Infection with P. vivax, confirmed by microscopy.
  3. Age 3 years or older (no restriction on upper age limit).
  4. Written or witnessed verbal consent obtained from the patient or the patients parent or guardian.
  5. Married women of child bearing age confirmed to be non-pregnant at outset and willing to remain thus for the duration of the study.
  6. Willingness to comply with the requirements of the protocol and particularly to provide venous and thumb prick blood samples.
  7. Available for follow up for the duration of the study and not less than 6 months.
  8. 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.
  9. Availability of G6PD status by willingness to be tested at admission.

Exclusion Criteria:

  1. General condition requiring hospital admission.
  2. Evidence of any concomitant infection likely to mask treatment response at the time of presentation.
  3. Presence of any other underlying disease that compromises the diagnosis and the evaluation of the response to the study medication.
  4. 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.
  5. Known methaemoglobin reductase deficiency and haemoglobin M.
  6. 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.
  7. Visible jaundice.
  8. Use of an investigational drug within 30 days or 5 half-lives whichever is the longer.
  9. Severe anaemia (Hb<7 g/dl).
  10. Other species of malaria seen.
  11. Pregnancy, assessed by pregnancy test in all married women of child-bearing age (age over 14 and under 50).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Day 14 slide clearance rate (complete clearance of parasites), assessed by microscopists who are blind to treatment allocation.

Secondary Outcome Measures

Outcome Measure
Adverse events.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

London School of Hygiene and Tropical Medicine

Collaborators

HealthNet TPO

Investigators

  • Principal Investigator: Christopher Whitty, FRCP, LSHTM
  • Study Director: Mark Rowland, PhD, LSHTM

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2004

Study Completion (ACTUAL)

March 1, 2006

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (ESTIMATE)

September 12, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

January 12, 2017

Last Update Submitted That Met QC Criteria

January 11, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITDCKD45

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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