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Trial registered on ANZCTR


Registration number
ACTRN12623000344695
Ethics application status
Approved
Date submitted
17/02/2023
Date registered
31/03/2023
Date last updated
31/03/2023
Date data sharing statement initially provided
31/03/2023
Date results information initially provided
31/03/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artemether-lumafantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum in two sentinel sites in Togo
Scientific title
Efficacy and safety of artemether-lumafantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum in children aged 6 to 59 months at two sentinel sites in Togo
Secondary ID [1] 308974 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 328987 0
Condition category
Condition code
Infection 325970 325970 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 or dihydroartemisinin-piperaquine. Artemether-lumefantrine tablets (containing 20 mg artemether+ 120 mg lumefantrine in each tablet) was 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 body weight (bw)of artemether and 29-144 mg/kg bw of lumefantrine. For dihydroartemisinin-piperaquine, 4mg/kg body weight (bw) dihydroartemisinin+18mg/kg bw piperaquine will be given.

Patients were sequentially enrolled: first to artemether-lumefantrine until the target sample was reached. Then the subsequent patients was enrolled to artemether-lumefantrine until the target sample was reached. All treatments was given orally under direct supervision by the health worker and patients were followed up for 28 days.Tablets were crushed and added to water in spoon and given to the child.
Intervention code [1] 325417 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333813 0
Proportion of treatment failures (early treatment failure + late clinical failure+late parasitological failure). This is a composite primary outcome.
Assessments were done clinically and parastologically using malaria microscopy. PCR analysis correction on blood samples to differentiate recrudescence from new infection. .
Timepoint [1] 333813 0
Days 0 (prior to treatment), 1, 2 (during treatment),3, 7, 14, 21, 28 (post-treatment) for artemether-lumefantrine

Days 0 (prior to treatment), 1, 2 (during treatment),3, 7, 14, 21, 28, 35 and 42 (post-treatment) for dihydroartemisinin-piperaquine
Secondary outcome [1] 418409 0
Percent of adverse event following treatment of artemether-lumefantrine or dihydroartesmisinin-piperaquine 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. Those for dihydroartemisinin include asthenia, cough, diarrhoea, fever, loss of appetite, nausea, vomiting.

Patients or care takers of children were asked on each visit about previous symptoms that have emerged since the previous follow-up visit. When clinically indicated, patients were assessed and treated appropriately. All adverse events will be recorded on the case report form.
Timepoint [1] 418409 0
Days 0 (prior to treatment), 1, 2 (during treatment),3, 7, 14, 21, 28 (post-treatment) for artemether-lumefantrine

Days 0 (prior to treatment), 1, 2 (during treatment),3, 7, 14, 21, 28, 35 and 42 (post-treatment) for dihydroartemisinin-piperaquine

Eligibility
Key inclusion criteria
• age from six to 59 months
• mono-infection with P. falciparum confirmed by positive blood smear (i.e. no mixed infection);
• parasitaemia of 2000–200,000 per micrometer asexual forms;
• Presence of axillary or tympanic temperature greater or equal to 37.5 degrees centigrade or history of fever during the past 24 h;
• ability to swallow oral medication;
• ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
• informed consent from parent or guardian.
Minimum age
6 Months
Maximum age
59 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• presence of general danger signs in children aged between 6 to 59 months or signs of severe falciparum malaria according to the definitions of WHO.
• weight under 5 kg;
• haemoglobin below 8 g per dl;
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• presence of severe malnutrition defined as a child who has symmetrical oedema involving at least the feet or has a mid-upper arm circumference below 110 mm in children greater.
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• regular medication, which may interfere with antimalarial pharmacokinetics;
• 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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation sheet designed for this purpose from a list of numbers randomly generated by a computer using the software (EPICALC 2000)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data was double entered by two independent data clerks using WHO database Excel programme, Data was analysed by both Kaplan-Meier and per-protocol methods. In addition to the reasons for withdrawal, patients were censored or excluded from the analysis if they were withdrawn or lost to follow-up or PCR results were 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:
• a description of all patients screened and the distribution of reasons for non-inclusion in the study;
• a description of all the patients included in the study;
• the proportion of adverse events and serious adverse events in all the patients included in the study;
• the proportion of patients lost to follow-up or withdrawn, with 95% confidence intervals and a list of reasons for withdrawal;
• the cumulative incidence of success and failure rates at day 28 (artemether-lumefantrine) or at day 42 (dihydroartemisinin-piperaquine), PCR-uncorrected and PCR-corrected; and
• the proportion of early treatment failure, late clinical failure, late parasitological failure and adequate clinical and parasitological response at day 28 for artemether-lumefantrine or day 42 for dihydroartemisinin-piperaquine, with 95% confidence intervals, PCR-uncorrected and PCR-corrected

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
14/09/2021
Date of last participant enrolment
Anticipated
Actual
18/12/2021
Date of last data collection
Anticipated
Actual
28/01/2022
Sample size
Target
352
Accrual to date
Final
357
Recruitment outside Australia
Country [1] 25255 0
Togo
State/province [1] 25255 0
Maritime and Plateau

Funding & Sponsors
Funding source category [1] 313188 0
Government body
Name [1] 313188 0
Ministère de la Santé de l’Hygiène Publique et de l’accès Universel aux Soins
Country [1] 313188 0
Togo
Primary sponsor type
Government body
Name
Ministère de la Santé de l’Hygiène Publique et de l’accès Universel aux Soins
Address
Rue Adame, Quartier administratif
BP 386 Lomé
Country
Togo
Secondary sponsor category [1] 314899 0
None
Name [1] 314899 0
Address [1] 314899 0
Country [1] 314899 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312422 0
Comité de Bioéthique pour la Recherche en Santé (CBRS)
Ethics committee address [1] 312422 0
Ministère de la Santé, Direction des Pharmacies,
Angle avenue Sarakawa et avenue du 2 Février, Lomé
Ethics committee country [1] 312422 0
Togo
Date submitted for ethics approval [1] 312422 0
01/04/2021
Approval date [1] 312422 0
01/05/2021
Ethics approval number [1] 312422 0
021/2021/CBRS 27 May 2021

Summary
Brief summary
Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum malaria infections in children aged 6 to 59 months in Togo was assessed. The treatments given under direct supervision and clinical and parasitological parameters were monitored for 28 days (artemether-lumefantrine) or 42 days (dihydroartemisinin-piperaquine) to establish proportion of patients with PCR corrected treatment failure and frequency of adverse events. Mutations in K13, mdr1, crt, dhfr an dhps genes were investigated on day 0 samples.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124606 0
Dr Monique A. DORKENOO
Address 124606 0
University of Togo, Faculty of Health Sciences
Boulevard Gnassingbé Eyadema
01BP1515 Lomé
Country 124606 0
Togo
Phone 124606 0
+22822204196
Fax 124606 0
Email 124606 0
monicadork@yahoo.fr
Contact person for public queries
Name 124607 0
Dr Monique A. DORKENOO
Address 124607 0
University of Togo, Faculty of Health Sciences
Boulevard Gnassingbé Eyadema
01BP1515 Lomé
Country 124607 0
Togo
Phone 124607 0
+22822204196
Fax 124607 0
Email 124607 0
monicadork@yahoo.fr
Contact person for scientific queries
Name 124608 0
Dr Marian Warsame
Address 124608 0
School of Public Health and Community Medicine
Medicinaregatan 18A
41390 Göteborg
Sweden
Country 124608 0
Sweden
Phone 124608 0
+46760525254
Fax 124608 0
Email 124608 0
marian.warsame@gu.se

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.