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Trial registered on ANZCTR


Registration number
ACTRN12622000873729
Ethics application status
Approved
Date submitted
22/05/2022
Date registered
20/06/2022
Date last updated
20/06/2022
Date data sharing statement initially provided
20/06/2022
Date results information initially provided
20/06/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artemether-lumefantrine for the treatment of
uncomplicated Plasmodium falciparum malaria in Nangarhar and
Laghman, Afghanistan
Scientific title
Efficacy and safety of artemether-lumefantrine for the treatment of
uncomplicated Plasmodium falciparum malaria in Nangarhar and
Laghman, Afghanistan.
Secondary ID [1] 307189 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Malaria 326414 0
Condition category
Condition code
Infection 323698 323698 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This was one arm prospective study to assess the efficacy and safety of artemether-lumefantrine (containing 20 mg artemether+ 120 mg lumefantrine in each tablet) given twice daily for three days according to 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. The total target dose ranges were 5-24 mg/kg bw of artemether and 29-144 mg/kg bw of lumefantrine. All treatments was given orally under direct supervision by the health worker. The patients were followed up for 28 days
Intervention code [1] 323639 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331448 0
Percent of treatment failures (early treatment failure + late clinical failure+late parasitological failure). This is a composite primary outcome.

Enrolled patients was monitored for parasitological (using microscopy) and clinical responses. PCR analysis was used to differentiate recrudescence from new infection. Treatment outcomes was classified according to the latest WHO protocol.
Timepoint [1] 331448 0
Days 0(before treatment), 1, 2,3, 7, 14, 21, 28
(primary endpoint)
Secondary outcome [1] 410306 0
Percent of adverse event following treatment.
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.

Parents or guardians of all enrolled 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 [1] 410306 0
On days 1, 2, 3, 7, 14, 21, 28

Eligibility
Key inclusion criteria
1. Aged between 6 months and above with the exception of 12-17 years old female minors and unmarried females above 18 years and above;
2. Mono-infection with P. falciparum detected by microscopy;
3. Parasitaemia of 500 – 200000 per microL asexual forms;
4. Presence of axillary or tympanic temperature greater or equal to 37.5 degrees 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 18 years;
8. Informed assent from any minor participant aged from 12 to 17 years; and
9. Consent for pregnancy testing from married female aged 18 years and above
Minimum age
6 Months
Maximum age
No limit
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 malaria according to the definitions of WHO;
2. Weight under 5 kg;
3. Haemoglobin below 8 g per dl;
4. Mixed or mono-infection with another Plasmodium species detected by microscopy;
5. Presence of severe malnutrition defined as a child aged 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 of married women aged 18 years and above; and
10. Unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age and who are 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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 area is assumed 5%, 5% has been chosen. At a confidence level of 95% and a precision around the estimate of 10%, with a 20% increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 60 patients should be included in the study per site

Data analysis
WHO excel software program was used for data management and analysis. Data was analysed by two methods: the Kaplan-Meier method and per-protocol analysis. Patients was considered withdrawn from the analysis if the PCR results were unclassifiable or if the results of PCR indicate that the failure was due to reinfection with P. falciparum.
The final analysis included:
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 282, 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
Actual
19/09/2019
Date of last participant enrolment
Anticipated
Actual
4/12/2019
Date of last data collection
Anticipated
Actual
31/12/2019
Sample size
Target
120
Accrual to date
Final
123
Recruitment outside Australia
Country [1] 24783 0
Afghanistan
State/province [1] 24783 0
Laghman and Nangarhar

Funding & Sponsors
Funding source category [1] 311495 0
Government body
Name [1] 311495 0
Ministry of Public Health Afghanistan
Country [1] 311495 0
Afghanistan
Primary sponsor type
Government body
Name
Ministry of Public Health Afghanistan
Address
Sehat-e-Ama Square, Wazir Akbar khan Road, Kabul, Afghanistan
Country
Afghanistan
Secondary sponsor category [1] 312895 0
None
Name [1] 312895 0
None
Address [1] 312895 0
None
Country [1] 312895 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310955 0
Institutional Review Board (IRB) of Afghanistan at Public Health Istitute
Ethics committee address [1] 310955 0
Central polyclinic of Kabul, Kabul
Central Blood Bank 5& 6 Floors, building Cinema Pamir area, Kabul
Ethics committee country [1] 310955 0
Afghanistan
Date submitted for ethics approval [1] 310955 0
20/06/2019
Approval date [1] 310955 0
30/07/2019
Ethics approval number [1] 310955 0
IRB Code No: A.0719.0051

Summary
Brief summary
Febrile malaria patients aged 6 months and above was recruited to assess efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infection. Artemether-lumefantrine was given based on weight bands: one tablet to those weighing 5-14kg; 2 tablets for 15-24 kg; 3 tablets for 25-34 kg and four tablets for equal to or greater than 35 kg. Clinical and parasitological parameters were monitored for 28 days follow-up to establish proportion of patients with PCR corrected treatment failure, frequency of adverse events and polymorphism of molecular markers for artemisinin resistance (K13).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119486 0
Dr Mohammad Sami Nahzat
Address 119486 0
National Malaria and Leishmania Control Programme,
Darul Aman Road Sanatorium Street, Kabul 25000
Country 119486 0
Afghanistan
Phone 119486 0
+93700216 0046
Fax 119486 0
Email 119486 0
[email protected]
Contact person for public queries
Name 119487 0
Mohammad Sami Nahzat
Address 119487 0
National Malaria and Leishmania Control Programme,
Darul Aman Road Sanatorium Street, Kabul 25000
Country 119487 0
Afghanistan
Phone 119487 0
+93700216 0046
Fax 119487 0
Email 119487 0
[email protected]
Contact person for scientific queries
Name 119488 0
Marian Warsame
Address 119488 0
School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg
Box 463, 405 30 Göteborg, Sweden
Country 119488 0
Sweden
Phone 119488 0
+46760525254
Fax 119488 0
Email 119488 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.