Assessing the Efficacy of Four Drug Combinations as the Next First-Line Therapy for Uncomplicated Malaria in Malawi - Full Text View

Sponsors and Collaborators:	Centers for Disease Control and Prevention Ministry of Health and Population, Malawi
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00164710

Purpose

Sulfadoxine-pyrimethamine (SP) is the current first-line treatment for uncomplicated malaria in Malawi. The malaria parasite P. falciparum has developed resistance to this drug so that the drug is much less effective than in previous years. This study was developed and conducted in collaboration with the National Malaria Control Programme of Malawi to assess the efficacy of four antimalarial drug combinations to provide evidence to assist the Malawian Ministry of Health in identifying and implementing as policy the next first-line antimalarial for uncomplicated malaria in Malawi. In an open, randomized trial in children under five years of age, four drug combinations, all of which are licensed in Malawi, are being assessed: amodiaquine plus sulfadoxine-pyrimethamine (AQ-SP), amodiaquine plus artesunate (AQ-Art), chlorproguanil-dapsone plus artesunate (CD-Art) and lumefantrine-artemether (LA). SP is also included as a fifth arm of the study for current data on its efficacy. Data on side effects of the drugs will also be collected. The results of this study will provide some of the information necessary to guide the Malawi National Malaria Control Program in selecting its next first antimalarial treatment for uncomplicated malaria. The study adheres to the World Health Organization's 2003 standardized protocol for assessing antimalarial drug efficacy.

Condition	Intervention	Phase
Malaria, Falciparum	Drug: sulfadoxine-pyrimethamine Drug: amodiaquine plus sulfadoxine-pyrimethamine Drug: amodiaquine plus artesunate Drug: chlorproguanil-dapsone plus artesunate Drug: lumefantrine-artemether	Phase IV

MedlinePlus related topics: Malaria

Drug Information available for: Pyrimethamine Sulfadoxine Artesunate Fansidar Artemether Benflumetol Dapsone Amodiaquine Amodiaquine hydrochloride Chlorproguanil

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	An Open Randomised Trial of the Efficacy of Sulfadoxine-Pyrimethamine (SP), Amodiaquine + SP (AQ-SP), AQ + Artesunate (AQ-Art), Chlorproguanil-Dapsone + Art (CD-Art), and Lumefantrine-Artemether (LA) for Uncomplicated Malaria in Malawi

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

• Rate of Adequate Clinical and Parasitological Response at 14 days (WHO-defined measure of efficacy)

Secondary Outcome Measures:

• Rate of Adequate clinical and parasitological response 28 days
• Mean percent change in blood haemoglobin concentration between day 0 and day 28
• Incidence of adverse events during the period of observation
• Rate of Early Treatment Failure (as defined by the WHO in their 2003 standardized protocol for assessing antimalarial drug efficacy)
• Rate of Late Clinical Failure (as defined by the WHO)
• Rate of Late Parasitologic Failure (as defined by the WHO)
• Percent of patients with a decrease in haemoglobin concentration
• Percent of patients with a decrease in haemoglobin concentration of ≥ 2g/dl
• Prevalence of parasitemia on Day 2
• Prevalence of parasitemia on Day 3
• Gametocyte prevalence on Day 14
• Gametocyte prevalence on Day 28

Estimated Enrollment:	365
Study Start Date:	April 2005
Estimated Study Completion Date:	September 2005

Eligibility

Ages Eligible for Study:	6 Months to 59 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Children age 6 – 59 months
Axillary temperature ≥ 37.5 °C
Monoinfection with P. falciparum
Parasitaemia between 2000 – 200000 parasites/µl
Haemoglobin concentration (finger-prick blood sample by HemoCue) > 7g/dl
Consent by the patient’s adult guardian
Residence in the locality and willingness to attend for scheduled visits

Exclusion Criteria:

altered consciousness
convulsions
prostration (inability to sit/stand/suck/drink)
respiratory distress or breathlessness
jaundice
abnormal breathing
haemoglobinuria
circulatory collapse
persistent vomiting (cannot keep down liquids)
evidence of a diagnosis other than malaria on physical examination
presence of mixed infection
presence of severe malnutrition (as evidenced by symmetrical oedema involving at least the feet, light hair color, or cachexia)
contraindications to the antimalarial drugs used, especially history of allergy
history of receiving a drug with antimalarial activity in the week prior to enrollment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164710

Locations

Malawi, Lilongwe District
Kawale Health Center
Lilongwe, Lilongwe District, Malawi
Malawi, Machinga District
Machinga District Hospital
Liwonde, Machinga District, Malawi
Malawi, Nkhotakota District
Matiki Health Center
Dwangwa, Nkhotakota District, Malawi

Sponsors and Collaborators

Centers for Disease Control and Prevention

Ministry of Health and Population, Malawi

Investigators

Principal Investigator:

Rachel N Bronzan, MD, MPH

Centers for Disease Control and Prevention

More Information

Study ID Numbers:	CDC-NCID-4539, PA# 04018
Study First Received:	September 13, 2005
Last Updated:	September 13, 2005
ClinicalTrials.gov Identifier:	NCT00164710
Health Authority:	United States: Federal Government; Malawi: National Health Sciences Research Committee

Keywords provided by Centers for Disease Control and Prevention:

antimalarials

Study placed in the following topic categories:

Pyrimethamine
Artesunate
Benflumetol
Protozoan Infections
Sulfadoxine-pyrimethamine
Amodiaquine
Clotrimazole
Miconazole
Tioconazole

Malaria
Sulfadoxine
Malaria, Falciparum
Artemether
Folic Acid
Chloroguanide
Dapsone
Parasitic Diseases
Chlorproguanil

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Antiplatyhelmintic Agents
Coccidiosis
Anthelmintics
Enzyme Inhibitors
Anti-Infective Agents, Urinary
Renal Agents
Folic Acid Antagonists

Schistosomicides
Pharmacologic Actions
Antimalarials
Anti-Bacterial Agents
Antiparasitic Agents
Antifungal Agents
Therapeutic Uses
Amebicides
Coccidiostats
Leprostatic Agents

ClinicalTrials.gov processed this record on January 16, 2009