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Trial registered on ANZCTR


Registration number
ACTRN12623000241639
Ethics application status
Approved
Date submitted
21/10/2022
Date registered
6/03/2023
Date last updated
6/03/2023
Date data sharing statement initially provided
6/03/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of the efficacy and safety of Artemether +Lumefantrine (Coartem®) with low-dose Primaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in three sites of Savanakhet, Salavanh, and Attopue province, Lao PDR (2022)
Scientific title
Evaluation of the efficacy and safety of Artemether +Lumefantrine (Coartem®) with low-dose Primaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in three sites of Savanakhet, Salavanh, and Attopue province, Lao PDR 2022)
Secondary ID [1] 308240 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 328003 0
Condition category
Condition code
Infection 325063 325063 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study is a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria. Artemether-lumefantrine drug combination will be administered for 3 days according to body weight a total of 6 doses, weight groups: 5-14kg= 1 tablet twice daily for 3 days; 15-14kg = 2 tablets twice daily for 3 days; 25-34kg= 3 tablets twice daily for 3 days; and 35kg and above = 4 tablets twice daily for 3 days. The target dose range: a total dose of 5-24mg/kg bw of artemether and 29-144mg/kg bw of lumefantrine. Detail dosage tablet can be seen in annex 3 of the attached study protocol. Primaquine treatment will be administered as a tablet for oral mode. Primaquine will be administered as a single 15-mg adult dose ( 0.25mg base/kg) on day 0 for uncomplicated P.falciparum cases, and once daily (0.25mg base /kg) for 14 days for G6PD normal or weekly dose (0.75mg base /kg) for 8 weeks for G6PD deficiency P.vivax case. for treatment of uncomplicated P.falciparum and P.vivax malaria and monitored for 28 days
measurement at baseline ( day 0 before dosing ) and on days 1,2,3,7,14,21,28. The following up of malaria vivax radical treatment compliance scheme had been existing in sub-district level including community level. Communication mechanism set up with following up from was developed and used, and reporting / refering of potential adverse event case to higher facility management.
Intervention code [1] 324703 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332891 0
All 3 primary outcomes such as "The proportion of patients with early treatment failure'; "late clinical failure"; and "late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy" will be assessed as a composite primary outcomes, not assess independently.
These outcome will be assessed under appointment of regular clinical and parasitological re-assessment, which focus on temperature check for any fever detection then blood films will be made for apprearance, density of parasites, and collection of blood as dry blood spot (DBS) for further PCF and molecular mapping, especially on day, 2, 3, 7 then weekly for remainder of the follow-up period. Patients will be advised to return on any days during the follow-up period if symptoms return and not to wait for the next schedule visit day.
The DBS will be collected on D0 (and day of faillure) to study the polymorphism or copy mubers of Pfmdr1, pfatp6, and pfcrt gene, which are considered as marker of resistance to artemether -Lumefantrine. The technique used will be polymerase chain reation (PCR).the test will be done at the WHO reference laboratory of Pasteur Institute, Cambodia.
Timepoint [1] 332891 0
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 will be assessed daily on Day 0,1,2 and 3, then weekly there after in D7, D14, D21, until Day 28. Patient is reminded to return on any day during the follow-up period if symptoms return and not to wait for the next scheduled visit day.
Secondary outcome [1] 414999 0
To determine the polymorphism of molecular markers for artemisinine resistance.
to assessment of this, dried blood spot will be collected for Polymerase Chain Reaction (PCR) analysis
Timepoint [1] 414999 0
Patient will be follow-up according to appointment visit on D1, D2, D3, D7, D14, D21, and D28. patient will be adviced to return on any day if they have symptoms. per visit, patient are required to undergo reqular clinical and parasitological assessment.

Eligibility
Key inclusion criteria
• aged 6 months up to 60 years old;
• mono-infection with P. falciparum and P. vivax confirmed by positive blood smear (no mixed infection);
• P. falciparum parasitaemia of 250-100,000/µl asexual forms;
• P. vivax parasitaemia of 250-60,000/µl asexual forms
• presence of axillary temperature equal or more than 37.5 °C 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; and
• Informed consent from the patient or from a parent or guardian in the case of children.
• informed assent from any minor participant aged from 12 to 18 years; and
• consent for pregnancy testing from female of child-bearing age (defined as age > 12 years and sexually active).
Minimum age
6 Months
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO );
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• presence of severe malnutrition (defined as a child whose growth standard is below –3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
• 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);
• 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);
• Women age 12-18 years old
• a positive pregnancy test or lactating
• Unable to or unwilling to take contraceptives for pregnancy negative married women of child- bearing age.

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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/10/2022
Date of last participant enrolment
Anticipated
30/07/2023
Actual
Date of last data collection
Anticipated
30/08/2023
Actual
Sample size
Target
300
Accrual to date
33
Final
Recruitment outside Australia
Country [1] 25076 0
Lao People's Democratic Republic
State/province [1] 25076 0
Savannakhet, Salavanh, Attapeu

Funding & Sponsors
Funding source category [1] 312498 0
Other
Name [1] 312498 0
World Health Organization
Country [1] 312498 0
Lao People's Democratic Republic
Primary sponsor type
Government body
Name
Ministry of Health
Address
Samsanthai road, Ban Thatkhao, Sisattanak district, Vientiane Capital
Country
Lao People's Democratic Republic
Secondary sponsor category [1] 314086 0
None
Name [1] 314086 0
Address [1] 314086 0
Country [1] 314086 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311832 0
National Ethics Committee for Health Research
Ethics committee address [1] 311832 0
Samsanthai road, Ban Khaoyot, Sisattanak district, Vientiane Capital
Ethics committee country [1] 311832 0
Lao People's Democratic Republic
Date submitted for ethics approval [1] 311832 0
30/04/2022
Approval date [1] 311832 0
10/08/2022
Ethics approval number [1] 311832 0
062/NECHR

Summary
Brief summary
Evaluation of the efficacy and safety of Artemether+ Lumefantrine (Coartem®) with low-dose Primaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in three sites of Savanakhet, Salavanh, and Attopue province, Lao PDR.
To assess the efficacy of current first line treatment policy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum and P. vivax malaria infections.
Study Sites: Three provinces of Savanakhet (5 districts of Phin, Sepon, Nong, Vilabury, and Thapangtong), Salavanh (2 provincial hospitals (public and Military) and 3 districts of Samouai, Taoi and Toumlan), and Attopue (4 districts of Phouvong, Sansay, Sanamsay, and Saysetha; and 1 Military hospital)
Study Period: From August 2022 to September 2023
Study Design: This surveillance study is a one arm prospective study
Patient population: Febrile patients aged between 6 months and 60, with confirmed uncomplicated P. falciparum and P. vivax infection, except females aged 12-18 years old, as it is culturally sensitive to request pregnancy test for young unmarried women.
Sample Size: Total of 300 patients to be enrolled 150 P.falciparum and 150 P.vivax cases. Each study site/province will recruit 100 cases, in which 50 cases maximum of P.falciparum and 50 cases maximum of P.vivax)
Treatment(s) and follow-up: Artemether-lumefantrine drug combination (Artemether 20mg / lumefantrine 120 mg per tablet), twice a day will be administered over 3 days according to body weight to a total of 6 doses. Primaquine will be administered as a single 15-mg adult dose (0.25 mg base/kg) on day 0 for uncomplicated P. falciparum cases, and once daily (0.25 base/kg) for 14 days for G6PD normal or weekly dose (0.75 base/kg) for 8 weeks for G6PD deficient P. vivax cases. The correct drug dosage will be determined from the dosing chart . 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
Exploratory endpoints: to determine the polymorphism of molecular markers for artemisinin resistance.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122530 0
Dr KEOBOUPHAPHONE CHINDAVONGSA
Address 122530 0
Center Of Malariology, Parasitology and Entomology, Nongdouang road, Ban Khoualuang tai, Chanthaboury district, Vientiane Capital
Country 122530 0
Lao People's Democratic Republic
Phone 122530 0
+856 20 55617339
Fax 122530 0
+856 21 218131
Email 122530 0
[email protected]
Contact person for public queries
Name 122531 0
Boualam Khamlom
Address 122531 0
Center Of Malariology, Parasitology and Entomology, Nongdouang road, Ban Khoualuang tai, Chanthabooury district, Vientiane Capital
Country 122531 0
Lao People's Democratic Republic
Phone 122531 0
+856 20 58249269
Fax 122531 0
+856 21 218131
Email 122531 0
[email protected]
Contact person for scientific queries
Name 122532 0
Maniphone Khanthavong
Address 122532 0
Center Of Malariology, Parasitology and Entomology, Nongdouang road, Ban Khoualuang tai, Chanthabooury district, Vientiane Capital
Country 122532 0
Lao People's Democratic Republic
Phone 122532 0
+856 20 22402253
Fax 122532 0
+856 21 218131
Email 122532 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After analysis we will share to Stakeholders
When will data be available (start and end dates)?
Start 1/10/2022 and end 30/8/2023
Available to whom?
World Health Organization and Ministry of Health
Available for what types of analyses?
The EPI-INFO 6.0 software from USA and Excel sheet program (according to the Informal consultation on monitoring P. falciparum and P. vivax resistance to antimalarial drugs in the Mekong regions, September 2007 instructions) 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 withdraw
How or where can data be obtained?
The data be obtained from participant enrolment in Case record form and follow up patient on Day 0,1,2,3,7,14,21,28 and this data is available by emailing the principal investigator ([email protected] )


What supporting documents are/will be available?




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.