Combination Antimalarials in Uncomplicated Malaria

This study has been completed.
Sponsor:
Collaborators:
World Health Organization
Medical Research Council, South Africa
Global Fund
Information provided by:
University of Cape Town
ClinicalTrials.gov Identifier:
NCT00203801
First received: August 29, 2005
Last updated: September 7, 2006
Last verified: August 2005
  Purpose

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 Intervention
Malaria
Drug: Sulfadoxine-pyrimethamine
Drug: Artesunate plus sulfadoxine-pyrimethamine
Drug: Artemether-lumefantrine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University of Cape Town:

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 GLURP and 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 DHFR and 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

Estimated Enrollment: 700
Study Start Date: January 2002
Estimated Study Completion Date: July 2005
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.

  Eligibility

Ages Eligible for Study:   12 Months and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00203801

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

No publications provided

ClinicalTrials.gov Identifier: NCT00203801     History of Changes
Other Study ID Numbers: SEACAT 01 Mono (Am 1,2,3,5,6)
Study First Received: August 29, 2005
Last Updated: September 7, 2006
Health Authority: South Africa: Medicines Control Council
Mozambique: Ministry of Health
Swaziland: Ministry of Health and Social Welfare

Keywords provided by University of Cape Town:
Malaria
Efficacy
Pharmacokinetic
Gametocyte
Molecular markers
Sulfadoxine-pyrimethamine
Artesunate
Artemisinin

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Artemether-lumefantrine combination
Artesunate
Fanasil, pyrimethamine drug combination
Lumefantrine
Pyrimethamine
Sulfadoxine
Amebicides
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014