Combination Antimalarials in Uncomplicated Malaria

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Malaria	Drug: Sulfadoxine-pyrimethamine; Drug: Artesunate plus sulfadoxine-pyrimethamine; Drug: Artemether-lumefantrine	Not Applicable

Detailed Description:

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 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 Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	700 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open Label In Vivo Drug Study to Evaluate Combination Anti-Malarial Therapy (CAT),in Terms of Therapeutic Efficacy, Prevalence of Gametocyte Carriage and Prevalence of Molecular Markers Associated With SP Resistance in Uncomplicated Plasmodium Falciparum Infections.
Study Start Date :	January 2002
Study Completion Date :	July 2005

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Therapeutic efficacy defined as:
2. 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);
3. Sensitive or parasitological failure (RI, early and late, RII, RIII)
4. Parasitological failures will be classified as recrudescence or re-infection (or indeterminate) using GLURP and MSP I & II markers;
5. Parasite clearance time;
6. Fever clearance time.

Secondary Outcome Measures :

1. Association between study treatment and gametocyte carriage
2. Pharmacokinetics by measurement of whole blood levels of Sulfadoxine and Pyrimethamine, and lumefantrine should a reliable assay become available
3. Correlation of frequency of DHFR and DHPS mutations with parasitological outcome
4. Tolerability by describing adverse events and changes in haematological parameters
5. Capacity by describing the training and development of study teams and their subsequent skills attained

Eligibility Criteria

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Ages Eligible for Study:	12 Months and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 37.50C 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.
• 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 (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).

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Mozambique
Bela Vista Clinic
Bela Vista, Matutuine, Mozambique
Namaacha Clinic
Namaacha, Mozambique
South Africa
Ndumo Clinic
Ndumo, KwaZulu Natal, South Africa
Lulekani Clinic
Lulekani, Limpopo, South Africa
Naas Clinic
Naas, Mpumalanga, South Africa
Swaziland
Ndzevane Clinic
Ndzevane, Swaziland
Vuvulane Clinic
Vuvulane, Swaziland

Sponsors and Collaborators

University of Cape Town

World Health Organization

Medical Research Council, South Africa

Global Fund

Investigators

Principal Investigator:	Karen Barnes, MBChB	University of Cape Town

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00203801 History of Changes
Other Study ID Numbers:	SEACAT 01 Mono (Am 1,2,3,5,6)
First Posted:	September 20, 2005
Last Update Posted:	September 11, 2006
Last Verified:	August 2005

Keywords provided by University of Cape Town:

Malaria; Efficacy; Pharmacokinetic; Gametocyte	Molecular markers; Sulfadoxine-pyrimethamine; Artesunate; Artemisinin

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases; Artesunate; Lumefantrine; Artemether; Pyrimethamine; Sulfadoxine; Artemether-lumefantrine combination; Artemisinins; Fanasil, pyrimethamine drug combination; Amebicides; Antiprotozoal Agents	Antiparasitic Agents; Anti-Infective Agents; Antimalarials; Antifungal Agents; Coccidiostats; Schistosomicides; Antiplatyhelmintic Agents; Anthelmintics; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Urinary; Renal Agents