Clinical trial NCT01599000: Artemether-Lumefantrine Clinical Effectiveness Study
Official title: Artemether-Lumefantrine Clinical Effectiveness Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parasitologically Confirmed; Malarial
Keywords: malaria
Plasmodium
Papua New Guinea
artemether/lumefantrine
Lead sponsor: Papua New Guinea Institute of Medical Research
Sponsor class: OTHER_GOV
Collaborators: name: Australian Agency for International Development
name: National Department of Health, Papua New Guinea
First posted: 2012-05-15
Enrollment: 159
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Adequate Clinical and Parasitological Response (ACPR)
timeFrame: 42 days
Secondary outcomes:
Other outcomes:
Locations:
city: Alotau
country: Papua New Guinea
facility: Gurney Health Centre
state: Milne Bay
Study officials:
affiliation: Papua New Guinea Institute of Medical Research
name: Manuel W Hetzel, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Walter and Eliza Hall Institute of Medical Research
name: Mueller Ivo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Papua New Guinea Institute of Medical Research
name: Peter M Siba, PhD
role: PRINCIPAL_INVESTIGATOR
References: