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Trial registered on ANZCTR


Registration number
ACTRN12616001680459
Ethics application status
Approved
Date submitted
20/02/2015
Date registered
6/12/2016
Date last updated
6/12/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of Artemether - Lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in in sentinel sites in Mozambique.
Scientific title
Efficacy and safety of Artemether - Lumefantrine for the treatment of children with uncomplicated Plasmodium falciparum malaria in in sentinel sites in Mozambique.
Secondary ID [1] 286222 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 294268 0
Condition category
Condition code
Infection 294587 294587 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To assess the efficacy and safety of artemether/lumefantrine (20mg/120mg: 3 day regimen of twice daily dose of 1 tablet for 5-14 kg; 2 tablets for 15-24 Kg) for the treatment of uncomplicated P. falciparum infection. The treatment will be taken orally under direct supervision by the health worker. Eligibile subjects will be treated for three days and followed up for 28 days.
Intervention code [1] 291238 0
Treatment: Drugs
Comparator / control treatment
N/A
This is a surveillance prospective study of one-arm.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294356 0
Percent of treatment failures (early treatment failure + late clinical failure + late parasitological failure). This is composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy), clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 294356 0
At day 28 following initiation of artemether+lumefantrine treatment.
Secondary outcome [1] 313093 0
Percent of adverse event will be documented. The known adverse events of artemether/lumefantrine are abdominal discomfort, nausea, headache and dizziness.

Parents or guardians of all enrolled patients will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit. When clinically indicated, patients will be evaluated and treated appropriately. All adverse events will be recorded on the case report form.
Timepoint [1] 313093 0
At day 28 following initiation of treatment
Secondary outcome [2] 313094 0
Prevalence of artemisinin resistance molecular markers (K13).

Parasite DNA extracted from the dried blood spots will be analyzed by PCR and sequencing for the presence of K13 (molecular marker for artemisinin resistance).
Timepoint [2] 313094 0
At Day 0 (prior initiation of treatment)

Eligibility
Key inclusion criteria
1. age from 6 to 59 months;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 2000 – 200000 asesual/microliter asexual forms;
4. presence of axillary temperature greater than or equal to 37.5 degree centigrade or history of fever during the past 24 h;
5. ability to swallow oral medication;
6. ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
7. informed consent from parent or guardian
Minimum age
6 Months
Maximum age
59 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the latest definitions of WHO;
2. weight under 5 kg;
3. mixed or mono-infection with another Plasmodium species detected by microscopy;
4. presence of severe malnutrition defined as a child aged 6-60 months who has a mid-upper arm circumference < 115 mm);
5. presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
6. regular medication, which may interfere with antimalarial pharmacokinetics, (see appendix 2 for detailed list of prohibited medication during the study
7. history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients aged 6 to 59 months with uncomplicated malaria who met the study inclusion criteria were enrolled, treated on site with artemether/lumefantrine and monitored for
28 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
This surveillance study was one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria with
artemether/lumefantrine.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Currently the treatment failure rate to artemether+lumefantrine in the study area is less than 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients must be included per drug test. With a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 88 patients should be included in the study per treatment arm per site.

Excel WHO tailored database will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6679 0
Mozambique
State/province [1] 6679 0
Northern Region, Central Region, Southern Region

Funding & Sponsors
Funding source category [1] 290786 0
Government body
Name [1] 290786 0
Ministry of Health of Mozambique
Address [1] 290786 0
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Country [1] 290786 0
Mozambique
Primary sponsor type
Government body
Name
Ministry of Health
Address
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Country
Mozambique
Secondary sponsor category [1] 289470 0
None
Name [1] 289470 0
Nil
Address [1] 289470 0
Nil
Country [1] 289470 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292417 0
Comite Nacional de Bioethica para a Saude
Ethics committee address [1] 292417 0
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Ethics committee country [1] 292417 0
Mozambique
Date submitted for ethics approval [1] 292417 0
Approval date [1] 292417 0
16/12/2014
Ethics approval number [1] 292417 0
IRB00002657

Summary
Brief summary
Title: Efficacy and safety of Artemether - Lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in in sentinel sites in Mozambique.

Purpose: To assess the efficacy and safety of the current first line treatment policy;

Objective: To assess the efficacy and safety of Artemether - Lumefantrine for the treatment of uncomplicated P. falciparum malaria infections.

Study Sites: Cabo-Delgado in the northern region; Tete and Sofala in the Central region and Gaza in the Southern region of Mozambique.

Study Period: The study will be conducted from March to August 2015.

Study Design: One arm prospective study.

Patient population: Febrile patients aged 6 to 59 months, with confirmed uncomplicated P. falciparum infection.

Sample Size: 88 patients will be enrolled in each site.
Treatment(s) and follow-up: Artemether - Lumefantrine twice daily dose for three days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.

Primary endpoints: The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
Secondary endpoints: The frequency and nature of adverse events.

Optional exploratory endpoints:
to determine the polymorphism of molecular markers for name of artemisinin resistance;
Trial website
Nil
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 55154 0
Dr Sonia Enosse
Address 55154 0
Instituto Nacional de Saude, Ministerio da Saude, Mocambique
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Country 55154 0
Mozambique
Phone 55154 0
+258829690090
Fax 55154 0
Email 55154 0
enossesonia@gmail.com
Contact person for public queries
Name 55155 0
Dr Sonia Enosse
Address 55155 0
Instituto Nacional de Saude, Ministerio da Saude, Mocambique
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Country 55155 0
Mozambique
Phone 55155 0
+258829690090
Fax 55155 0
Email 55155 0
enossesonia@gmail.com
Contact person for scientific queries
Name 55156 0
Dr Sonia Enosse
Address 55156 0
Instituto Nacional de Saude, Ministerio da Saude, Mocambique
Central District, 1008 Avenue Eduardo Mondlane, Maputo, 1100
Country 55156 0
Mozambique
Phone 55156 0
+258829690090
Fax 55156 0
Email 55156 0
enossesonia@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary