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

Malaria, Falciparum Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00164710
• Other study ID #: CDC-NCID-4539
• Secondary ID: PA# 04018
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: September 26, 2012
• Start date: April 2005
• Est. completion date: September 2005

Study information

• Verified date: September 2012
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentMalawi: National Health Sciences Research Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: September 2005
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 59 Months

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• sulfadoxine-pyrimethamine

• amodiaquine plus sulfadoxine-pyrimethamine

• amodiaquine plus artesunate

• chlorproguanil-dapsone plus artesunate

• lumefantrine-artemether

Locations

Country	Name	City	State
Malawi	Matiki Health Center	Dwangwa	Nkhotakota District
Malawi	Kawale Health Center	Lilongwe	Lilongwe District
Malawi	Machinga District Hospital	Liwonde	Machinga District

Sponsors (2)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Ministry of Health and Population, Malawi

Country where clinical trial is conducted

Malawi, 

Outcome

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