Assessing the Efficacy of Four Drug Combinations as the Next First-line Therapy for Uncomplicated Malaria in Malawi

NCT00164710 | Completed Phase 4

• 2 other identifiers: CDC-NCID-4539PA# 04018
• Study Type: interventional
• Target: 365
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Malaria, Falciparum

Keywords

antimalarials

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (12)

• • 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)

Interventions

sulfadoxine-pyrimethamine DRUG

amodiaquine plus sulfadoxine-pyrimethamine DRUG

amodiaquine plus artesunate DRUG

chlorproguanil-dapsone plus artesunate DRUG

lumefantrine-artemether DRUG

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Ministry of Health and Population, Malawi: collaborator

Study Sites (3)

Kawale Health Center

Lilongwe, Lilongwe District, Malawi

Location

Machinga District Hospital

Liwonde, Machinga District, Malawi

Location

Matiki Health Center

Dwangwa, Nkhotakota District, Malawi

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

fanasil, pyrimethamine drug combination; Amodiaquine; Artesunate; chloroguanil, dapsone drug combination; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Artemether; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Rachel N Bronzan, MD, MPH

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 14, 2005
• Study Start: April 1, 2005
• Primary Completion: September 1, 2005
• Study Completion: September 1, 2005
• Last Updated: September 27, 2012

Record last verified: 2012-09

Locations

MA (3)