Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001223224
Ethics application status
Approved
Date submitted
16/07/2018
Date registered
20/07/2018
Date last updated
5/11/2019
Date data sharing statement initially provided
5/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of Artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in five sites in 2017, Eritrea
Scientific title
Efficacy and safety of Artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in five sites in 2017, Eritrea
Secondary ID [1] 295572 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 308846 0
Condition category
Condition code
Infection 307776 307776 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The objective of the study was to assess the efficacy and safety of artemether+lumefantrine (20 mg/120 mg in each tablet) twice daily doses for three days for the treatment of uncomplicated falciparum malaria. The dose was 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] 301870 0
Treatment: Drugs
Comparator / control treatment
No comparator. It was single arm prospective study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306766 0
Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This was composite primary outcome.
Timepoint [1] 306766 0
Days 0, 1, 2, 3, 7, 14, 21, 28 (primary time point)
Secondary outcome [1] 349535 0
Percent of adverse event following treatment of artemether+lumefantrine.
The known adverse events of artemetherr+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.
Patients or Parents/guardians were asked routinely about previous symptoms and about symptoms that had emerged since the previous follow-up visit. When clinically indicated, patients was evaluated and treated appropriately. All adverse events was recorded on the case report form.
Timepoint [1] 349535 0
Days 0, 1, 2, 3, 7, 14, 21, 28
Secondary outcome [2] 349536 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). The sample analysis is in process
Timepoint [2] 349536 0
Day 0

Eligibility
Key inclusion criteria
1. age 6 months and above;
2. mono-infection with P. falciparum confirmed by positive blood smear (i.e. no mixed infection);
3. parasitaemia of 250-200 000 asexual forms per microliter;
4. presence of axillary temperature greater 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 the patient or from a parent or guardian in the case of children aged less than 18;
8. informed assent from any minor participant aged from 12 to 18 years; and
9. consent for pregnancy testing from female of child-bearing age (defined as age above 12 years and sexually active) and from their parent or guardian if under the age of 18 years.
Minimum age
6 Months
Maximum age
70 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 malaria according to the definitions of WHO;
2. weight under 5 kg;
3. haemoglobin below 8 g per deciliter;
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 < 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
As the treatment failure rate to artemether+lumefantrine in the areas was 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. Patients was 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 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
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
15/09/2017
Date of last participant enrolment
Anticipated
Actual
1/01/2018
Date of last data collection
Anticipated
Actual
28/03/2018
Sample size
Target
440
Accrual to date
Final
212
Recruitment outside Australia
Country [1] 10659 0
Eritrea
State/province [1] 10659 0
Gash Barka and Semenawi Keyh Bahri

Funding & Sponsors
Funding source category [1] 300148 0
Government body
Name [1] 300148 0
Ministry of Health, Eritrea
Country [1] 300148 0
Eritrea
Primary sponsor type
Government body
Name
Ministry of Health, Eritrea
Address
P.O. Box 212 Asmara, Eritrea
Country
Eritrea
Secondary sponsor category [1] 299551 0
None
Name [1] 299551 0
Address [1] 299551 0
Country [1] 299551 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300980 0
Health Research Proposal Review and Ethical Clearance
Ethics committee address [1] 300980 0
Ethics committee country [1] 300980 0
Eritrea
Date submitted for ethics approval [1] 300980 0
25/05/2017
Approval date [1] 300980 0
06/06/2017
Ethics approval number [1] 300980 0
HRPREC_6/6/2017

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85502 0
Dr Araia Berhane
Address 85502 0
Ministry of Health,
P. O. Box 212 Asmara
Country 85502 0
Eritrea
Phone 85502 0
+2911117041
Fax 85502 0
Email 85502 0
[email protected]
Contact person for public queries
Name 85503 0
Araia Berhane
Address 85503 0
Ministry of Health,
P. O. Box 212 Asmara
Country 85503 0
Eritrea
Phone 85503 0
+2911117041
Fax 85503 0
Email 85503 0
[email protected]
Contact person for scientific queries
Name 85504 0
Araia Berhane
Address 85504 0
Ministry of Health,
P. O. Box 212 Asmara
Country 85504 0
Eritrea
Phone 85504 0
+2911117041
Fax 85504 0
Email 85504 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
SourceTitleYear of PublicationDOI
Dimensions AIIncreasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea2023https://doi.org/10.1056/nejmoa2210956
N.B. These documents automatically identified may not have been verified by the study sponsor.