Artemether-Lumefantrine Clinical Effectiveness Study

In 2009, Papua New Guinea officially adopted artemether-lumefantrine (AL) as new national first-line drug for uncomplicated malaria. The principal purpose of this study is to measure the absolute effectiveness of AL when used under real-life clinical conditions, as compared to optimized in-vivo trial conditions. This question was raised by the National Department of Health in preparation for the country-wide roll-out of AL.

The study is designed as a randomized controlled trial comparing two study arms. Patients in the "effectiveness arm" receive the first dose of AL under full supervision in the clinic; the following doses will be taken at home, as in real-life clinical practice and according to the new national treatment guidelines. Patients in the "efficacy arm" will receive all doses of AL as directly observed treatment in the clinic in order to establish the efficacy of the drug when used under ideal conditions.

The study will enroll outpatients aged 6 months to 10 years with a history of fever and a positive rapid test for malaria. Patients meeting all enrollment criteria and providing full written informed consent by a parent/caretaker will be randomized into either of the two study arms. Patients in both arms will be followed up actively for 42 days. Patients in the efficacy arm will be scheduled for visits on days 0, 1, 2, 3, 7, 14, 28 and 42; patients in the effectiveness arm on days 0, 3, 7, 14, 28 and 42.

Study Overview

• Status: Completed
• Conditions: Parasitologically Confirmed; Malarial
• Intervention / Treatment: Drug: Artemether-lumefantrine combination

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 4

Contacts and Locations

Study Locations

• Papua New Guinea
  • Milne Bay
    • Alotau, Milne Bay, Papua New Guinea
      • Gurney Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 6 months to 10 years (+/- 1 month for children without known date of birth)
• Permanent resident in the study area
• Not enrolled in another study at the same time
• No known history of hypersensitivity reactions to artemether or lumefantrine
• History of fever in the previous 72 hours (approximate)
• Rapid diagnostic test (RDT) positive for any species of Plasmodium

Exclusion Criteria:

• General danger signs: inability to drink or breastfeed, vomiting everything, recent history of convulsions, lethargy or unconsciousness, inability to sit or stand up
• Signs of severe malaria (impaired consciousness, respiratory distress, circulatory collapse, abnormal bleeding, jaundice, or as determined by clinician)
• Severe malnutrition: defined as a child whose weight-for-height is below -3 standard deviation or less than 70% of the median of the NCHS/WHO normalized reference values, or who has symmetrical oedema involving at least the feet; or middle upper arm circumference under 12 cm
• Clinically significant concomitant disease requiring admission
• Contraindications mentioned in the national treatment guidelines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Efficacy arm; Supervised administration of six doses of fixed-dose artemether-lumefantrine (Coartem, Novartis)	Drug: Artemether-lumefantrine combination; fixed-dose tablet, six doses over three days, according to weight group; Other Names: Coartem, Novartis
Experimental: Effectiveness arm; Un-supervised administration of six doses of fixed-dose artemether-lumefantrine (Coartem, Novartis)	Drug: Artemether-lumefantrine combination; fixed-dose tablet, six doses over three days, according to weight group; Other Names: Coartem, Novartis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adequate Clinical and Parasitological Response (ACPR)	ACPR = Absence of parasitemia on Day 42 irrespective of axillary temperature without previously meeting any of the criteria of Early Treatment Failure or Late Clinical Failure or Late Parasitological Failure (adapted from WHO 2003).	42 days

Collaborators and Investigators

• Sponsor: Papua New Guinea Institute of Medical Research
• Collaborators: National Department of Health, Papua New Guinea; Australian Agency for International Development
• Investigators: Principal Investigator: Peter M Siba, PhD, Papua New Guinea Institute of Medical Research; Principal Investigator: Manuel W Hetzel, PhD, Papua New Guinea Institute of Medical Research; Principal Investigator: Mueller Ivo, PhD, Walter and Eliza Hall Institute of Medical Research

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 1, 2012
• First Submitted That Met QC Criteria: May 11, 2012
• First Posted (Estimate): May 15, 2012

Study Record Updates

• Last Update Posted (Estimate): August 16, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: malaria; artemether/lumefantrine; Plasmodium; Papua New Guinea
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: MRAC.09.13