Malaria
Conditions
Keywords
Malaria, Efficacy, Pharmacokinetic, Gametocyte, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin
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.
Interventions
DRUGSulfadoxine-pyrimethamine
Sponsors
World Health Organization
Medical Research Council, South Africa
University of Cape Town
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fever clearance time | — |
| 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 | — |
Secondary
| Measure | 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 | — |
Countries
Mozambique
Outcome results
None listed