Combination Antimalarials in Uncomplicated Malaria

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00203801
• Other study ID #: SEACAT 01 Mono (Am 1,2,3,5,6)
• Status: Completed
• Phase: N/A
• Start date: January 2002
• Est. completion date: July 2005

Study information

• Verified date: October 2018
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: July 2005
• Est. primary completion date: July 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months and older

Eligibility

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).

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Sulfadoxine-pyrimethamine

• Artesunate plus sulfadoxine-pyrimethamine

• Artemether-lumefantrine

Locations

Country	Name	City	State
Mozambique	Bela Vista Clinic	Bela Vista	Matutuine
Mozambique	Namaacha Clinic	Namaacha
South Africa	Lulekani Clinic	Lulekani	Limpopo
South Africa	Naas Clinic	Naas	Mpumalanga
South Africa	Ndumo Clinic	Ndumo	KwaZulu Natal
Swaziland	Ndzevane Clinic	Ndzevane
Swaziland	Vuvulane Clinic	Vuvulane

Sponsors (4)

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

Countries where clinical trial is conducted

Mozambique,  South Africa,  Swaziland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Therapeutic efficacy defined as:
Primary	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 glutamate-rich protein (GLURP) and merozoite surface protein (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, and lumefantrine should a reliable assay become available
Secondary	Correlation of frequency of dihydropteroate synthase (DHFR) and dihydrofolate reductase (DHPS) mutations with parasitological outcome
Secondary	Tolerability by describing adverse events and changes in haematological parameters
Secondary	Capacity by describing the training and development of study teams and their subsequent skills attained