Combination Antimalarials in Uncomplicated Malaria

N/ACompletedNCT00203801

University of Cape Town700 enrolled

Overview

The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.

The resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to the control of malaria. In the South East African Combination Anti-malarial Therapy (SEACAT) evaluation, there will be a comprehensive evaluation of phased introduction of combination anti-malarials (CAT) in Mozambique, Swaziland and South Africa. In order to facilitate formulation of an effective regional drug policy and provide a database for decision-making on the implementation of combination therapy, it is essential that the in vivo response to CAT in all three countries be investigated. An SP therapeutic efficacy study will be conducted according to this modified World Health Organization (WHO) protocol to guide the selection of CAT. After CAT is introduced an in vivo CAT efficacy study will then be conducted to evaluate the efficacy of artesunate plus SP (or artemether-lumefantrine in KwaZulu Natal and Limpopo). In areas of low intensity malaria transmission the CAT in vivo study results will be compared across sites and with those found at baseline with monotherapy, for each site.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

700

Conditions

Malaria

Interventions

Sulfadoxine-pyrimethamineDRUG

Artesunate plus sulfadoxine-pyrimethamineDRUG

Artemether-lumefantrineDRUG

Eligibility

Sex: ALLMin age: 12 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female, older than 12 months. * Weight \> 10 kg. * Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia of up to 250 000 asexual parasite/mcl blood with axillary temperature of greater than and equal to 37.5 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. * 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 Glucose-6-phosphate dehydrogenase (G6PD) deficiency (not a contra-indication for artemether-lumefantrine). * 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. artemether-lumefantrine).

Locations (7)

Ndzevane Clinic

Ndzevane, Eswatini

Vuvulane Clinic

Vuvulane, Eswatini

Bela Vista Clinic

Bela Vista, Matutuine, Mozambique

Namaacha Clinic

Namaacha, Mozambique

Outcomes

Primary Outcomes

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 glutamate-rich protein (GLURP) and merozoite surface protein (MSP) I & II markers;

Parasite clearance time;

Fever clearance time.

Secondary Outcomes

Association between study treatment and gametocyte carriage

Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine, and lumefantrine should a reliable assay become available

Correlation of frequency of dihydropteroate synthase (DHFR) and dihydrofolate reductase (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 and their subsequent skills attained

Data from ClinicalTrials.gov

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