A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria

Malaria Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00203814
• Other study ID #: SEACAT 01a ASSP
• Status: Completed
• Phase: N/A
• First received: September 13, 2005
• Last updated: November 15, 2006
• Start date: January 2004
• Est. completion date: March 2005

Study information

• Verified date: August 2005
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mozambique: Ministry of Health (MISAU)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Sulfadoxine-pyrimethamine

• Artesunate plus sulfadoxine-pyrimethamine

Locations

Country	Name	City	State
Mozambique	Boane Clinic	Boane	Maputo
Mozambique	Magude Clinic	Magude

Sponsors (3)

Lead Sponsor	Collaborator
University of Cape Town	Medical Research Council, South Africa, World Health Organization

Country where clinical trial is conducted

Mozambique, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Sensitive or parasitological failure (RI, early and late, RII, RIII)
Primary	Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers
Primary	Parasite clearance time
Primary	Fever clearance time
Secondary	Association between study treatment and gametocyte carriage
Secondary	Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine
Secondary	Correlation of the frequency of DHFR and DHPS mutations with parasitological outcome
Secondary	Tolerability by describing adverse events and changes in haematological parameters
Secondary	Capacity building by describing the training and development of study teams and their subsequent skills attained