Clinical trial NCT00203814: 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
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: Malaria
Efficacy
Pharmacokinetic
Gametocyte
Molecular markers
Sulfadoxine-pyrimethamine
Artesunate
Artemisinin
Lead sponsor: University of Cape Town
Sponsor class: OTHER
Collaborators: name: World Health Organization
name: Medical Research Council, South Africa
First posted: 2005-09-20
Enrollment: 280
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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)
measure: Sensitive or parasitological failure (RI, early and late, RII, RIII)
measure: Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers
measure: Parasite clearance time
measure: Fever clearance time
Secondary outcomes:
measure: Association between study treatment and gametocyte carriage
measure: Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine
measure: Correlation of the frequency of DHFR and DHPS mutations with parasitological outcome
measure: Tolerability by describing adverse events and changes in haematological parameters
measure: Capacity building by describing the training and development of study teams and their subsequent skills attained
Other outcomes:
Locations:
city: Boane
country: Mozambique
facility: Boane Clinic
state: Maputo
city: Magude
country: Mozambique
facility: Magude Clinic
Study officials:
affiliation: University of Cape Town
name: Karen Barnes, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
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.