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Trial registered on ANZCTR


Registration number
ACTRN12618001224213
Ethics application status
Approved
Date submitted
17/07/2018
Date registered
20/07/2018
Date last updated
5/11/2019
Date data sharing statement initially provided
5/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum in Afgoye site and Plasmodium vivax in Bosaso site, Somalia
Scientific title
Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum in Afgoye site and Plasmodium vivax in Bosaso site, Somalia
Secondary ID [1] 295575 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 308860 0
Condition category
Condition code
Infection 307782 307782 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The objective of the study is to assess the efficacy and safety of artemether+lumefantrine (20 mg/120 mg in each table) twice daily doses for three days for the treatment of uncomplicated falciparum (Afgoye site) and vivax (Bosaso site) malaria. The dose regimens for both Plasmodium and vivax infection will be calculated based on the recommended weight bands as follows: 1 tablet to those weighing 5 to 14 kg; 2 tablets for 15 to 24 kg; 3 tablets for 25 to 34 kg and 4 tablets for equal or greater than 35 kg.

All treatments will be taken orally under direct supervision by the health worker and will be followed up for 28 days.
Intervention code [1] 301873 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306769 0
Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This is composite primary outcome.
Study patients will be evaluated for parasitological and clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 306769 0
Days 0, 1, 2, 3, 7, 14, 21, 28
Primary outcome [2] 306770 0
Percent of adverse event following treatment of artemether+lumefantrine will be investigated.
The known adverse events of atemether+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.

Patients or care takers of children 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 [2] 306770 0
Days 0, 1, 2, 3, 7, 14, 21, 28
Secondary outcome [1] 349538 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 [1] 349538 0
Day 0 (before treatment is given)

Eligibility
Key inclusion criteria
1. age between 6 months and 60 years with the exception of 12-17years old female minors and unmarried females 18 years and above;
2. mono-infection with P. falciparum (Afgoye site) or P. vivax (Bosaso site) confirmed by positive blood smear (i.e. no mixed infection);
3. parasitaemia of 500 - 200000 per microliter asexual forms;
4. presence of axillary temperature greater or equal to 37.5 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 the patient or from a parent or guardian in the case of children aged less than age of majority;
8. informed assent from any minor participant aged from 12 to age of majority years; and
9. consent for pregnancy testing from female of child-bearing age (defined as age below 12 years and sexually active) and from their parent or guardian if under the age of majority years.
Minimum age
6 Months
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. presence of general danger signs in children aged under 12 years or signs of severe falciparum or vivax malaria according to the definitions of WHO;
2. female aged from 12 years and age of majority;
3. weight under 5 kg;
4. mixed or mono-infection with another Plasmodium species detected by microscopy;
5. presence of severe malnutrition defined as a child aged between 6-60 months who has a mid-upper arm circumference below 115 mm);
6. 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);
7. regular medication, which may interfere with antimalarial pharmacokinetics;
8. history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);
9. a positive pregnancy test or breastfeeding; and
10. unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age (defined as age above 12 years and sexually active).

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)
No concealment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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
Sample size estimation
As the treatment failure rate to artemether+lumefantrine in the areas is estimated to 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients will be included. With a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 88 patients per site will be included in the study.

Analysis of data
The WHO excel software programs will be used for data management and analysis. Data will be analyzed by two methods: the Kaplan-Meier method and per-protocol analysis. Subjects will be considered withdrawn from the analysis if the PCR results are unclassifiable or if the results of PCR indicate that the failure is due to reinfection with other species.The final analysis will include:

1. a description of all patients screened and the distribution of reasons for non-inclusion in the study;
2. a description of all the patients included in the study;
3. the proportion of adverse events and serious adverse events in all the patients included in the study;
4. the proportion of patients lost to follow-up or withdrawn, with 95% confidence intervals and a list of reasons for withdrawal;
5. the cumulative incidence of success and failure rates at day 28, PCR-uncorrected and PCR-corrected; and
6. the proportion of early treatment failure, late clinical failure, late parasitological failure and adequate clinical and parasitological response at day 28, with 95% confidence intervals, PCR-uncorrected and PCR-corrected.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/08/2018
Actual
29/12/2018
Date of last participant enrolment
Anticipated
31/03/2019
Actual
23/02/2019
Date of last data collection
Anticipated
28/04/2019
Actual
23/03/2019
Sample size
Target
176
Accrual to date
Final
85
Recruitment outside Australia
Country [1] 10660 0
Somalia
State/province [1] 10660 0
North East and Lower Shabelle regions

Funding & Sponsors
Funding source category [1] 300150 0
Other
Name [1] 300150 0
World Health Organization Count Office Somalia
Country [1] 300150 0
Somalia
Primary sponsor type
Other
Name
World Health Organization Count Office Somalia
Address
Bulo Hubey Airport Street 1
Mogadishu
Country
Somalia
Secondary sponsor category [1] 299553 0
None
Name [1] 299553 0
Address [1] 299553 0
Country [1] 299553 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300982 0
WHO Research Ethics Review Committee
Ethics committee address [1] 300982 0
20 Avenue Appia -
CH-1211 Geneva
Ethics committee country [1] 300982 0
Switzerland
Date submitted for ethics approval [1] 300982 0
25/06/2018
Approval date [1] 300982 0
12/07/2018
Ethics approval number [1] 300982 0
ERC.0003074

Summary
Brief summary
Title: Efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated Plasmodium falciparum in Afgoye site and Plasmodium vivax in Bosaso site, Somalia
Purpose: To assess the efficacy of current first-line treatment.
Objective: To assess the efficacy and safety of artemether+lumefantrine for the treatment of uncomplicated P. falciparum and P. vivax, Somalia.
Study Sites: Afgoye for P. falciparum and Bosaso for P. vivax.
Study Period: From July 2018 to April 2019
Study Design: One arm prospective study.
Patient population: Febrile patients aged between 6 months and 60 years, inclusive, with confirmed uncomplicated P. falciparum or P. vivax infection. Female minors aged 12-17 years and unmarried females aged 18 years and above will be excluded as subjecting them to pregnancy testing is unacceptable according to the local customs and cultures.
Sample Size: A total of 88 patients will be enrolled in each site.
Treatment(s) and follow-up: Artemether+lumefantrine twice daily for 3 days will be evaluated. 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
• proportion of polymorphism of molecular markers for artemisinin resistance (K13)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85510 0
Mr Abdullahi Mohamed Hassan
Address 85510 0
Minitry of Health and Human Services
Wadajir, Km5, Zope Street
Mogadishu
Country 85510 0
Somalia
Phone 85510 0
+252615500514
Fax 85510 0
Email 85510 0
[email protected]
Contact person for public queries
Name 85511 0
Abdullahi Mohamed Hassan
Address 85511 0
Minitry of Health and Human Services
Wadajir, Km5, Zope Street
Mogadishu
Country 85511 0
Somalia
Phone 85511 0
+252615500514
Fax 85511 0
Email 85511 0
[email protected]
Contact person for scientific queries
Name 85512 0
Abdullahi Mohamed Hassan
Address 85512 0
Minitry of Health and Human Services
Wadajir, Km5, Zope Street
Mogadishu
Country 85512 0
Somalia
Phone 85512 0
+252615500514
Fax 85512 0
Email 85512 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.