Combination Antimalarials in Uncomplicated Malaria

Sponsor

University of Cape Town (Other)

Overall Status

Completed

CT.gov ID

NCT00203801

Collaborator

World Health Organization (Other), Medical Research Council, South Africa (Other), Global Fund (Other)

700

Enrollment

Locations

Duration (Months)

100

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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	N/A

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 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 Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Label Study to Evaluate Combination Anti-malarial Therapy,in Terms of Efficacy, Prevalence of Gametocyte Carriage and Molecular Markers Associated With Sulfadoxine Pyrimethamine Resistance in Uncomplicated Plasmodium Falciparum

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Jul 1, 2005

Actual Study Completion Date :

Jul 1, 2005

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country
1	Bela Vista Clinic	Bela Vista	Matutuine	Mozambique
2	Namaacha Clinic	Namaacha		Mozambique
3	Ndumo Clinic	Ndumo	KwaZulu Natal	South Africa
4	Lulekani Clinic	Lulekani	Limpopo	South Africa
5	Naas Clinic	Naas	Mpumalanga	South Africa
6	Ndzevane Clinic	Ndzevane		Swaziland
7	Vuvulane Clinic	Vuvulane		Swaziland