Combination Antimalarials in Uncomplicated Malaria

• ClinicalTrials.gov Identifier: NCT00203801
• Recruitment Status: Completed
• First Posted: September 20, 2005
• Last Update Posted: October 19, 2018
• Sponsor: University of Cape Town
• Collaborators: World Health Organization; Medical Research Council, South Africa; Global Fund
• Information provided by (Responsible Party): Professor Karen I Barnes, University of Cape Town

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	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 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 (Clinical Trial)
• Enrollment: 700 participants
• 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: January 2002
• Actual Primary Completion Date: July 2005
• Actual Study Completion Date: July 2005

Arms and Interventions

Outcome Measures

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 glutamate-rich protein (GLURP) and merozoite surface protein (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 dihydropteroate synthase (DHFR) and dihydrofolate reductase (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

• Ages Eligible for Study: 12 Months and older (Child, Adult, Older Adult)
• 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 37.5 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

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

• Responsible Party: Professor Karen I Barnes, University of Cape Town
• ClinicalTrials.gov Identifier: NCT00203801
• Other Study ID Numbers: SEACAT 01 Mono (Am 1,2,3,5,6)
• First Posted: September 20, 2005
• Last Update Posted: October 19, 2018
• Last Verified: October 2018

Keywords provided by Professor Karen I Barnes, 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 Drug Combination; Fanasil, pyrimethamine drug combination; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Schistosomicides; Antiplatyhelmintic Agents; Anthelmintics; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Urinary; Renal Agents