Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day

NCT ID: NCT02020330

Last Updated: 2018-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-25
• Study Completion Date: 2015-03-25

Brief Summary

This is a randomised two arm study, comparing artemether-lumefantrine 3 days and 5 days treatment. Patients will be randomised in blocks of ten to one of the two treatment arms. The standard regimen is twice daily for three days with a delay of at least eight hours between the first and second doses. A single of primaquine will be given to all patients on the first day of treatment for gametocytocidal activity. The initial treatment will be given under supervision, all other subsequent doses will be given to the patient to the taken at home. Patients will be followed up for nine visits over forty two days.

Detailed Description

• The study will be conducted in 6 village health centres in the Mon and Kayin states
• The patient or parent/guardian (in case of minor or under aged) must personally sign and date the latest approved version of the informed consent form before any study specific procedures are performed
• A case record form will be completed for each patient documenting symptoms prior to clinic attendance, concomitant illness, drug history. Height, weight, vital signs and physical examination findings will be recorded.
• At enrolment (D0) all patients will have the following samples taken:

• Repeat parasite count (thick and thin films). Treatment should be started without waiting for the result.
• Filter paper blood blots (3 dots on Whatman 3MM filter paper approx 180-300 µL blood) for parasite genotyping (MSP1, MSP2, GLURP in case of recurrence during follow-up)
• Haemoglobin
• Laboratory procedures

• Slide microscopy: Thick and thin blood films stained with Giemsa will be read and counts expressed as the number of parasites per 500 white blood cells
• Molecular studies: The samples will be used to detect asexual parasites (blood smear, sensitive PCR), parasite population structure (Sequenom genotyping and sequencing), gametocytes (microscopy). The samples will be stored in a cool box and kept maximum 5 days in the field and will be transported to the local laboratory for processing. Plasma and buffy coat will be separated, frozen and stored. The frozen packed red cells will be transported to the molecular laboratory at MORU, Bangkok, Thailand, for sample processing (DNA extraction, quantitative PCRs).

Conditions

Plasmodium Falciparum Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AL3days

Artemether-lumefantrine 3 days

Group Type: ACTIVE_COMPARATOR

Artemether-lumefantrine 3 days

Intervention Type: DRUG

One tablet contains 20mg artemether and 120mg lumefantrine. The standard regimen is twice daily for 3 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 3 days arm.

AL5days

Artemether-lumefantrine 5 days

Group Type: EXPERIMENTAL

Artemether-lumefantrine 5 days

Intervention Type: DRUG

One tablet contains 20mg artemether and 120mg lumefantrine. The experiment regimen is twice daily for 5 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 5 days arm.

Interventions

Artemether-lumefantrine 3 days

One tablet contains 20mg artemether and 120mg lumefantrine. The standard regimen is twice daily for 3 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 3 days arm.

Intervention Type: DRUG

Artemether-lumefantrine 5 days

One tablet contains 20mg artemether and 120mg lumefantrine. The experiment regimen is twice daily for 5 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 5 days arm.

Intervention Type: DRUG

Other Intervention Names

Coartem®, Novatis, Switzerland; Coartem®, Novartis, Switzerland

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 6 year

2. Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°C

3. Microscopic confirmation of asexual stages of P. falciparum (may be mixed with non-falciparum species) with parasitaemia PFT≥5/500 WBC

4. Written informed consent given to participate in the trial

Exclusion Criteria

1. Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age unless menstruating).

2. Female of 12 to 18 years of age

3. P. falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).

4. Signs or symptoms indicative of severe malaria including:

• Impaired consciousness (Blantyre Coma Score <5 or Glasgow Coma Scale <15)
• Severe anaemia (Hb% <5 mg/dl)
• Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
• Respiratory distress
• Severe jaundice
• Haemodynamic shock

5. A full course of artemether-lumefantrine treatment in the previous 28 days

6. Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis

7. History of splenectomy

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Smithuis, MD

Role: PRINCIPAL_INVESTIGATOR

Myanmar Oxford Clinical Research Unit

Locations

Medical Action Myanmar

Yangon, , Burma

Countries

Burma

References

Tun KM, Jeeyapant A, Myint AH, Kyaw ZT, Dhorda M, Mukaka M, Cheah PY, Imwong M, Hlaing T, Kyaw TH, Ashley EA, Dondorp A, White NJ, Day NPJ, Smithuis F. Effectiveness and safety of 3 and 5 day courses of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar. Malar J. 2018 Jul 11;17(1):258. doi: 10.1186/s12936-018-2404-4.

Reference Type: DERIVED

PMID: 29996844 (View on PubMed)

Other Identifiers

MOCRU1301

Identifier Type: -

Identifier Source: org_study_id