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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Khyber district of Khyber Pakhtunkhwa and Zhob district of Balochistan Pakistan
Scientific title
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Khyber district of Khyber Pakhtunkhwa and Zhob district of Balochistan Pakistan
Secondary ID [1] 299686 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 315039 0
Condition category
Condition code
Infection 313369 313369 0 0
Studies of infection and infectious agents

Study type
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 are 5-24 mg/kg bw of artemether and 29-144 mg/kg bw of lumefantrine. All treatments will be given orally under direct supervision by the health worker. The patient will be followed up for 28 days
Intervention code [1] 315953 0
Treatment: Drugs
Comparator / control treatment
No control group as the study is a one arm cohort prospective study.
Control group

Primary outcome [1] 321850 0
Percent of treatment failures (early treatment failure + late clinical failure+late parasitological failure). This is a composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy) and clinical responses. Treatment outcomes will be classified according to the latest WHO protocol.
Timepoint [1] 321850 0
On days 1, 2, 3, 7, 14, 21, 28
Secondary outcome [1] 376471 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] 376471 0
On days 1, 2, 3, 7, 14, 21, 28
Secondary outcome [2] 376472 0
Prevalence of mutations of K13 (molecular marker for artemisinin resistance).

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] 376472 0
On day 0 (before treatment)

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
Both males and females
Can healthy volunteers participate?
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. 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 below 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;
7. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);
8. A positive pregnancy test or breastfeeding of married women aged 18 years and above; and
9. 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
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 4
Type of endpoint(s)
Statistical methods / analysis
Sample size estimation
The assumed treatment failure rate to artemether/lumefantrine in the area is 5%. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 73 patients must be included. 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 site.

Data analysis
WHO excel software program will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis. In addition to the reasons for withdrawal listed in section 3.8 of the protocol, patients 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 P. falciparum or P. vivax.
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 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 status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment outside Australia
Country [1] 21979 0
State/province [1] 21979 0
Khyber Pakhtunkhwa and Balochistan

Funding & Sponsors
Funding source category [1] 304164 0
Government body
Name [1] 304164 0
Ministry of National Health Services Regulations and Coordination
Address [1] 304164 0
Ground Floor, National Influenza Control Program Building,NIH, Chak Shahzad, Islamabad, Pakistan
Country [1] 304164 0
Funding source category [2] 304165 0
Name [2] 304165 0
World Health Organization
Address [2] 304165 0
20 Av. Appia,
1211 Geneva 27 Switzerland
Country [2] 304165 0
Primary sponsor type
Government body
Ministry of National Health Services Regulations and Coordination
Ground Floor, National Influenza Control Program Building,
NIH Premises, Park Road Chak Shahzad,
Zip Code 44000, Islamabad, Pakistan
Secondary sponsor category [1] 304392 0
Name [1] 304392 0
Address [1] 304392 0
Country [1] 304392 0

Ethics approval
Ethics application status
Ethics committee name [1] 304640 0
National Bioethics Committe (NBC) Pakistan
Ethics committee address [1] 304640 0
Pakistan Heaalh Research Council, Sharah-e-Jamhuriat
Off Constitution Avenue, Sector G-5/2, Islamabad, Pakistan
Ethics committee country [1] 304640 0
Date submitted for ethics approval [1] 304640 0
Approval date [1] 304640 0
Ethics approval number [1] 304640 0
No.4-87/NBC-101+255-Exten 2019-20/19/134

Brief summary
Febrile malaria patients aged 6 months and above will be recruited to assess efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infection. Artemether-lumefantrine will be 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 will be monitored for 28 days followed-up to establish proportion of patients with treatment failure, frequency of adverse events and polymorphism of molecular markers for artemisinin resistance (K13).
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 97686 0
Mr Mounir Ahmed Khan
Address 97686 0
Institute of Public Health, Quetta Balochistan province
Brewery Road. Provincial Malaria Reference Laboratory, IPH Quetta, Balochistan,
Country 97686 0
Phone 97686 0
Fax 97686 0
Email 97686 0
Contact person for public queries
Name 97687 0
Mr Mounir Ahmed Khan
Address 97687 0
Institute of Public Health, Quetta Balochistan province
Brewery Road. Provincial Malaria Reference Laboratory, IPH Quetta, Balochistan,
Country 97687 0
Phone 97687 0
Fax 97687 0
Email 97687 0
Contact person for scientific queries
Name 97688 0
Dr Marian Warsame
Address 97688 0
School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Country 97688 0
Phone 97688 0
Fax 97688 0
Email 97688 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Clinical study report
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5522 0
Ethical approval
Citation [1] 5522 0
Link [1] 5522 0
Email [1] 5522 0
Other [1] 5522 0
Attachment [1] 5522 0
Type [2] 5523 0
Clinical study report
Citation [2] 5523 0
Link [2] 5523 0
Email [2] 5523 0
Other [2] 5523 0
Attachment [2] 5523 0
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