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Trial registered on ANZCTR


Registration number
ACTRN12619000408189
Ethics application status
Approved
Date submitted
6/03/2019
Date registered
13/03/2019
Date last updated
5/03/2020
Date data sharing statement initially provided
13/03/2019
Type of registration
Prospectively 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, Champasack, and Salavanh province, Lao PDR.
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, Champasack, and Salavanh province, Lao PDR.
Secondary ID [1] 297640 0
None
Universal Trial Number (UTN)
None
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 311910 0
Condition category
Condition code
Infection 310492 310492 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Artemether-Lumefantrine(AL) drug combination (Artemether 20mg-Lumefantrine 120mg per tablet) will be administered daily for 3 days according to body weight for the treatment of uncomplecated pP.falciparum(P.f) and P.vivax (P.v) malaria. Both P.f and P.v patients will be administered AL according to the following dosage:
1). Patients between 5-14kg = 1 AL tablet will be given twice a day
2). Patients between 15-24kg = 2 AL tablets will be given twice a day
3). Patients between 25-34kg = 3 AL tablets will be given twice a day
4). Patients 35kg and above = 4 AL tablets will be given twice a day
In addition to AL, P.f cases will be given a single dose of 0.25mg/kg ( body weight) Primaquine(PQ) on the day of enrolment (D0). G6PD normal P.v cases will be given daily a PQ tablet ( 0.25mg/kg/day for 14 days start on D0. G6PD deficiency P.v patients will be given a weekly dose of PQ: 0.75mg/kg per week for 8 weeks start on D0. Doses of AL medicine will be administered under the supervision of a qualified member of the staff designated by principal investigater. The study patients will be observed for 30 minute aftter medicine administration for adverse reactions or vomiting. For P.f cases the single low dose will also be administered under supervision on D0. For G6PD normal P.v patients, PQ administration will be observed D0-D3 and D7. All other nine days, staff will follow up PQ administration by telephone and will confirm the number of remaining tablets at the following visit. For G6PD deficiency P.v patients, administration of PQ will be under supervision for the first 5 weeks , while the remaining 3 weeks will be follow up by telephone.
Intervention code [1] 313873 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319357 0
The study's primary outcome is the following composite outcome: 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.
Timepoint [1] 319357 0
28 days after treatment is the primary timepoint patient will be assessed daily on day 0,1,2 and 3 and weekly there after (D7;D14;D21) until Day 28
Secondary outcome [1] 367874 0
Evaluate safety by the incidence of adverse events assessed by clinical observation of symptoms For example vomitting, abdominal pain, and rashes
Timepoint [1] 367874 0
Any time adverse event occur between Day 0 and Day 28

Eligibility
Key inclusion criteria
• Aged 6 months and above;
• 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 greater than or equal to 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.
Minimum age
6 Months
Maximum age
No limit
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 (Appendix 1);
• 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
• the cumulative incidence of success and failure rates at day 28, 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, with 95% confidence intervals, PCR-uncorrected and PCR-corrected.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/04/2020
Actual
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
2/02/2021
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment outside Australia
Country [1] 21332 0
Lao People's Democratic Republic
State/province [1] 21332 0
savannakhet champasackn salavanh

Funding & Sponsors
Funding source category [1] 302170 0
Other
Name [1] 302170 0
World Health Organization
Country [1] 302170 0
Lao People's Democratic Republic
Primary sponsor type
Government body
Name
Ministry of Health
Address
Samsanthai road, Ban thatkhao, Siattanak district, Vientiane Capital
Country
Lao People's Democratic Republic
Secondary sponsor category [1] 302010 0
None
Name [1] 302010 0
Address [1] 302010 0
Country [1] 302010 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302851 0
National Ethics Committee for Health Research
Ethics committee address [1] 302851 0
Samsenthai road, Ban khaoyot, Sisattanak district, Vientiane Capital
Ethics committee country [1] 302851 0
Lao People's Democratic Republic
Date submitted for ethics approval [1] 302851 0
17/12/2018
Approval date [1] 302851 0
31/12/2019
Ethics approval number [1] 302851 0
098/NECHR

Summary
Brief summary
This surveillance study is a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria. , People with uncomplicated malaria who meet the study inclusion criteria will be enrolled, treated on site with the ACT artemether-lumefantrine for uncomplicated P. falciparum and P. vivax malaria and monitored for 28 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. On the basis of the results of these assessments, the patients will be classified as having therapeutic failure (early or late) or an adequate response. The proportion of patients experiencing therapeutic failure during the follow-up period will be used to estimate the efficacy of the study drug(s). PCR analysis will be used to distinguish between a true recrudescence/relapse due to treatment failure and episodes of reinfection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91610 0
Dr Bouasy Hongvanthong
Address 91610 0
Center of Malariology , Parasitology and Entomology, Nongdouang road, Ban khoualuang tai, Chanthaboury district, Vientiane Capital
Country 91610 0
Lao People's Democratic Republic
Phone 91610 0
+856 21 214040
Fax 91610 0
+ 856 21 218131
Email 91610 0
[email protected]
Contact person for public queries
Name 91611 0
Viengxay Vanisaveth
Address 91611 0
Center of Malariology , Parasitology and Entomology, Nongdouang road, Ban khoualuang tai, Chanthaboury district, Vientiane Capital
Country 91611 0
Lao People's Democratic Republic
Phone 91611 0
+856 21 214040
Fax 91611 0
+ 856 21 218131
Email 91611 0
[email protected]
Contact person for scientific queries
Name 91612 0
Keobouphaphone Chindavongsa
Address 91612 0
Center of Malariology , Parasitology and Entomology, Nongdouang road, Ban khoualuang tai, Chanthaboury district, Vientiane Capital
Country 91612 0
Lao People's Democratic Republic
Phone 91612 0
+856 21 214040
Fax 91612 0
+ 856 21 218131
Email 91612 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
IPD is recorded on a WHO analysis excel spreadsheet, but sharing of IPD for this trial will not occur.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1541Study protocol    377138-(Uploaded-06-03-2019-18-51-28)-Study-related document.doc
1542Ethical approval    377138-(Uploaded-28-02-2020-14-05-34)-Study-related document.pdf



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.