Combination Antimalarials in Uncomplicated Malaria

October 17, 2018 updated by: Professor Karen I Barnes, University of Cape Town

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment

700

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Fever clearance time.
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;

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cape Town

Collaborators

World Health Organization
Medical Research Council, South Africa
Global Fund

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Primary Completion (ACTUAL)

July 1, 2005

Study Completion (ACTUAL)

July 1, 2005

Study Registration Dates

First Submitted

August 29, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (ESTIMATE)

September 20, 2005

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2018

Last Update Submitted That Met QC Criteria

October 17, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SEACAT 01 Mono (Am 1,2,3,5,6)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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