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 compare the efficacy of sulfadoxine-pyrimethamine plus artesunate with that of sulfadoxine-pyrimethamine on its own for the treatment of uncomplicated malaria.

Detailed Description
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Resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to malaria control. In the South East African Combination Anti-malarial Therapy (SEACAT) evaluation, there is an evaluation of the phased introduction of combination anti-malarial therapy (CAT) in Mozambique, Swaziland and South Africa. In order to facilitate formulation of effective regional drug policy and provide a database for decision-making on the implementation of CAT, it is essential that the in vivo response to CAT be investigated. This will be achieved through the SEACAT 01 protocol which is a component of the SEACAT evaluation described in another file on this website. However, in selected Mozambique sites where the intensity of malaria transmission is high, a direct parallel group comparison of monotherapy (SP) with CAT (artesunate, AS, plus SP) will be conducted according to a specific amendment (Amendment 4) to the SEACAT 01 protocol. Amendment 4 is presented in this separate file on the website for clarity.

Official Title
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Open Label Drug Study (With Single and Parallel Group Components) to Evaluate Combination Antimalarial Therapy for Efficacy, Gametocyte Carriage and 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 uncomplicated acute P. falciparum malaria parasitaemia of up to 500 000 asexual parasite/mcl blood with axillary temperature of greater than and equal to 37.50C or history of fever. Documented informed consent. Lives close enough to the health centre for reliable follow up. Exclusion Criteria: Has received anti-malarial treatment in the past 7 days. Is infected with other malarial species (such subjects will be excluded retrospectively). 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). Has received cotrimoxazole or chloramphenicol in the past 7 days. History of G6PD deficiency. Is pregnant. Has a history of allergy to any sulphonamide (for SP) or artemisinin derivative (for artesunate and co-artemether).

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 frequency of DHFR and DHPS mutations with parasitological outcome |  |  | 
| Tolerability by describing adverse events and changes in haematological parameters |  |  | 
| Capacity by describing the training and development of study teams |  |  | 

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