A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Malaria

Intervention / Treatment
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* Drug: Sulfadoxine-pyrimethamine
* Drug: Artesunate plus sulfadoxine-pyrimethamine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sulfadoxine-pyrimethamine|nan|
|Drug: Artesunate plus sulfadoxine-pyrimethamine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gametocyte, Malaria, Efficacy, Pharmacokinetic, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin