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Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day (AL3vs5)

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ClinicalTrials.gov Identifier: NCT02020330
Recruitment Status : Completed
First Posted : December 24, 2013
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE October 30, 2013
First Posted Date  ICMJE December 24, 2013
Last Update Posted Date September 20, 2018
Actual Study Start Date  ICMJE November 25, 2013
Actual Primary Completion Date February 4, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2013)
proportion of patients with detectable parasitaemia [ Time Frame: On day 5 and day 7 ]
Assessed by sensitive PCR on days 5 and 7 after treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02020330 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2015)
  • Parasitaemia clearance time [ Time Frame: On day 3 and Day 5 ]
    Assessed by sensitive PCR on D3 in the 3 day arm and D5 in the 5 day arm
  • Gametocyte carriage rates [ Time Frame: Day 7 ]
  • artemether-lumefantrine tolerability [ Time Frame: 5 days ]
    Tolerability of artemether-lumefantrine will be assessed by comparing the proportion of patients with anorexia, nausea, vomiting, abdominal pain and other symptoms of administration between the intervention arm and the control arm
  • Comparison of effectiveness [ Time Frame: Day 42 ]
    Comparison of effectiveness uncorrected and corrected will be assessed by PCR genotyping
  • concentrations of lumefantrine [ Time Frame: Day 7 ]
  • Haematological recovery rate [ Time Frame: Day 28 ]
    Assessed by comparing hemoglobin between baseline and after treatment at day 28
  • Incidence of vivax malaria relapses [ Time Frame: 42 days ]
    Assessed by the microscopist find malaria smear positive within the follow up period
  • Comparison of addition of food supplement (fish oil) [ Time Frame: day 3 to day 21 ]
    Assessed by comparing lumefantrine concentration on day 7 and proportion of patients with detectable parasitaemia by qPCR
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2013)
  • Parasitaemia clearance time [ Time Frame: On day 3 and Day 5 ]
    Assessed by sensitive PCR on D3 in the 3 day arm and D5 in the 5 day arm
  • Gametocyte carriage rates [ Time Frame: Day 7 ]
  • artemether-lumefantrine tolerability [ Time Frame: 5 days ]
    Tolerability of artemether-lumefantrine will be assessed by comparing the proportion of patients with anorexia, nausea, vomiting, abdominal pain and other symptoms of administration between the intervention arm and the control arm
  • Comparison of effectiveness [ Time Frame: Day 42 ]
    Comparison of effectiveness uncorrected and corrected will be assessed by PCR genotyping
  • concentrations of lumefantrine [ Time Frame: Day 7 ]
  • Haematological recovery rate [ Time Frame: Day 28 ]
    Assessed by comparing hemoglobin between baseline and after treatment at day 28
  • Incidence of vivax malaria relapses [ Time Frame: 42 days ]
    Assessed by the microscopist find malaria smear positive within the follow up period
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day
Official Title  ICMJE An Open-label Randomized Controlled Trial to Evaluate the Effectiveness and Safety of a 3 Day Versus 5 Day Course of Artemether-lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Myanmar
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Plasmodium Falciparum Infection
Intervention  ICMJE
  • Drug: 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.
    Other Name: Coartem®, Novatis, Switzerland
  • 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.
    Other Name: Coartem®, Novartis, Switzerland
Study Arms  ICMJE
  • Active Comparator: AL3days
    Artemether-lumefantrine 3 days
    Intervention: Drug: Artemether-lumefantrine 3 days
  • Experimental: AL5days
    Artemether-lumefantrine 5 days
    Intervention: Drug: Artemether-lumefantrine 5 days
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 18, 2013)
150
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 25, 2015
Actual Primary Completion Date February 4, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Myanmar
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02020330
Other Study ID Numbers  ICMJE MOCRU1301
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frank Smithuis, MD Myanmar Oxford Clinical Research Unit
PRS Account University of Oxford
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP