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A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria

Primary Purpose

Malaria

Status
Completed
Phase
Not Applicable
Locations
Mozambique
Study Type
Interventional
Intervention
Sulfadoxine-pyrimethamine
Artesunate plus sulfadoxine-pyrimethamine
Sponsored by
University of Cape Town
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria focused on measuring Malaria, Efficacy, Pharmacokinetic, Gametocyte, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin

Eligibility Criteria

12 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female, older than 12 months. Weight > 10 kg. Diagnoses of pure uncomplicated acute P. falciparum malaria parasitaemia of up to 500 000 asexual parasite/mcl blood with axillary temperature of greater than or equal to 37.5°C or history of fever (defined as within the previous 24 hours). Documented informed consent. Lives close enough to the study site for reliable follow up. Exclusion Criteria: Has received anti-malarial treatment in the past 7 days. Is infected with other malarial species (such subjects may be excluded retrospectively from the analysis). Severely ill (based on WHO Criteria for severe malaria ) or if patient is considered, in the opinion of the investigator or designee, to have moderately severe malaria (e.g. prostrate, repeated vomiting, dehydrated) or other danger signs. Has received cotrimoxazole, trimethoprim, chloramphenicol, folate or tetracyclines (including doxycycline) in the past 7 days or is likely to require these during the study period. History of G6PD deficiency. Is pregnant or breastfeeding. Has a history of allergy to any of the study drugs (including other sulphonamides e.g. cotrimoxazole, other artemisinin derivatives e.g. co-artemether). Serious underlying disease that in the opinion of the clinic team and/or Principal Investigator would make the patient unsuitable for the study in terms of their safety or study analysis.

Sites / Locations

  • Boane Clinic
  • Magude Clinic

Outcomes

Primary Outcome Measures

Therapeutic efficacy defined as:Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Treatment Failure (LTF), defined as Late Clinical Failure (LCF) and Late Parasitological Failure (LPF)
Sensitive or parasitological failure (RI, early and late, RII, RIII)
Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers
Parasite clearance time
Fever clearance time

Secondary Outcome Measures

Association between study treatment and gametocyte carriage
Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine
Correlation of the frequency of DHFR and DHPS mutations with parasitological outcome
Tolerability by describing adverse events and changes in haematological parameters
Capacity building by describing the training and development of study teams and their subsequent skills attained

Full Information

First Posted
September 13, 2005
Last Updated
November 15, 2006
Sponsor
University of Cape Town
Collaborators
World Health Organization, Medical Research Council, South Africa
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1. Study Identification

Unique Protocol Identification Number
NCT00203814
Brief Title
A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria
Official Title
Open-Label, Randomised, Parallel Group in Vivo Drug Study to Evaluate Combination Anti-Malarial Therapy (CAT), Artesunate and Sulfadoxine-Pyrimethamine Versus Sulfadoxine-Pyrimethamine Alone, in Terms of Therapeutic Efficacy, Prevalence of Gametocyte Carriage and Prevalence of Molecular Markers Associated With SP Resistance In Uncomplicated Plasmodium Falciparum Infections.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2005
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2005 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
University of Cape Town
Collaborators
World Health Organization, Medical Research Council, South Africa

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine the efficacy of sulfadoxine-pyrimethamine plus artesunate versus sulfadoxine-pyrimethamine alone in the treatment of uncomplicated malaria.
Detailed Description
Resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to the control of malaria. In order to facilitate formulation of effective regional drug policies and to provide a database for decision-making on the implementation of combination therapy (CAT), it is essential that the in vivo response to CAT be investigated. In the South East African Combination Anti-malarial Therapy (SEACAT) evaluation, there is a comprehensive evaluation of the phased introduction of combination anti-malarial therapy in Mozambique. As a component of this evaluation, in selected Mozambique sites where intensity of malaria transmission is high, a direct parallel group comparison of monotherapy (SP) with CAT (artesunate plus SP) will be conducted according to this protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Malaria, Efficacy, Pharmacokinetic, Gametocyte, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
280 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Sulfadoxine-pyrimethamine
Intervention Type
Drug
Intervention Name(s)
Artesunate plus sulfadoxine-pyrimethamine
Primary Outcome Measure Information:
Title
Therapeutic efficacy defined as:Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Treatment Failure (LTF), defined as Late Clinical Failure (LCF) and Late Parasitological Failure (LPF)
Title
Sensitive or parasitological failure (RI, early and late, RII, RIII)
Title
Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers
Title
Parasite clearance time
Title
Fever clearance time
Secondary Outcome Measure Information:
Title
Association between study treatment and gametocyte carriage
Title
Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine
Title
Correlation of the frequency of DHFR and DHPS mutations with parasitological outcome
Title
Tolerability by describing adverse events and changes in haematological parameters
Title
Capacity building by describing the training and development of study teams and their subsequent skills attained

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, older than 12 months. Weight > 10 kg. Diagnoses of pure uncomplicated acute P. falciparum malaria parasitaemia of up to 500 000 asexual parasite/mcl blood with axillary temperature of greater than or equal to 37.5°C or history of fever (defined as within the previous 24 hours). Documented informed consent. Lives close enough to the study site for reliable follow up. Exclusion Criteria: Has received anti-malarial treatment in the past 7 days. Is infected with other malarial species (such subjects may be excluded retrospectively from the analysis). Severely ill (based on WHO Criteria for severe malaria ) or if patient is considered, in the opinion of the investigator or designee, to have moderately severe malaria (e.g. prostrate, repeated vomiting, dehydrated) or other danger signs. Has received cotrimoxazole, trimethoprim, chloramphenicol, folate or tetracyclines (including doxycycline) in the past 7 days or is likely to require these during the study period. History of G6PD deficiency. Is pregnant or breastfeeding. Has a history of allergy to any of the study drugs (including other sulphonamides e.g. cotrimoxazole, other artemisinin derivatives e.g. co-artemether). Serious underlying disease that in the opinion of the clinic team and/or Principal Investigator would make the patient unsuitable for the study in terms of their safety or study analysis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen Barnes, MBChB
Organizational Affiliation
University of Cape Town
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boane Clinic
City
Boane
State/Province
Maputo
Country
Mozambique
Facility Name
Magude Clinic
City
Magude
Country
Mozambique

12. IPD Sharing Statement

Citations:
PubMed Identifier
19558654
Citation
Allen EN, Little F, Camba T, Cassam Y, Raman J, Boulle A, Barnes KI. Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial. Malar J. 2009 Jun 26;8:141. doi: 10.1186/1475-2875-8-141.
Results Reference
derived

Learn more about this trial

A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria

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