Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001624178p
Ethics application status
Submitted, not yet approved
Date submitted
8/08/2019
Date registered
22/11/2019
Date last updated
22/11/2019
Date data sharing statement initially provided
22/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Therapeutic efficacy studies of artemisinin combination treatment (ACT) in Myanmar (2019)
Scientific title
Efficacy and safety artemether-lumefantrine and
dihydroartemisinin-piperaquine for the treatment of
uncomplicated Plasmodium falciparum malaria and chloroquine
for P. vivax in Buthidaung, Rakhine State
Secondary ID [1] 298973 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Malaria 313958 0
Condition category
Condition code
Infection 312363 312363 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To treat the confirmed Plasmodium falciparum malaria patients with artemether–lumefantrine; usual adult oral dose of 4 tabs (each tablet containing 20 mg artemether and 120 mg lumefantrine) twice daily for three days (a target dose 1.3/8 mg /kg twice daily for 3 days) or in dihydroartemisinin-piperaquine combination treatment - orally 3 tablets once (tablet containing 40mg dihydroartemisinin and 320 mg piperaquine phosphate ) per day for 3 days (target dose 2-2.4/16-19.2 mg/kg once a day for 3 days) will be given. Primaquine tablet (containing 7.5 mg ) will be given orally at the dose of 0.75 mg/kg as stat dose for all falciparum infected cases together with first dose of ACT(artemether-lumefantrine or dihydrortemisinin-piperaquine).
For confirmed Plasmodium vivax infected cases, chloroquine tablet (containing 150 mg base) will be given orally at the dose of 10mg/kg for day1 and day2, and 5mg/kg on day3 to have a total dose 25mg base/kg and it will be followed by radical curative treatment with primaquine tablet orally at the dose of 0.25mg base/kg/day for 14 days. If there is G6PD deficiency determined by G6PD RDT, primaquine will not be given.
Case recruitment will start with artemether-lumefantrine to get full sample size and it will be followed by dihydroartemesinin-piperaquine.
To monitor the adherence of ACT and chloroquine, the first dose will be administered at health center under observation of Research Medical Officer, and the following doses will be monitored by malaria volunteer health worker by recollecting the empty blisters daily. Primaquine in vivax infected patients will not be monitored.
Intervention code [1] 315238 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320990 0
Therapeutic efficacy of antimalarials (artemether-lumifantrine) , and dihydroartemisinin-piperaquine in Plasmodium falciparum and chloroquine in Plasmodium vivax malaria.
Treatment outcome will be categorized after 28 day follow up in artemether-lumifantrine, and chloroquine treated group and after 42 day follow up in dihydroartemisinin-piperaquine treated group applying WHO classification as follow;
Early treatment failure
• danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia;
• parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature;
• parasitaemia on day 3 with axillary temperature greater than or equal to 37.5 ºC;
• parasitaemia on day 3 is equal to or more than 25% of count on day 0.
Late treatment failure
Late clinical failure
• danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (day 42) in patients who did not previously meet any of the criteria of early treatment failure;
• presence of parasitaemia on any day between day 4 and day 28 with axillary temperature equal to or more than 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure
Late parasitological failure
• presence of parasitaemia on any day between day 7 and day 28 (day 42) with axillary temperature is less than < 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure
Adequate clinical and parasitological response
• absence of parasitaemia on day 28(day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure
Timepoint [1] 320990 0
At the end of 28 day follow up in artemether-lumifantrine treated group , and Chloroquine treated group, or at the end of 42 day follow up in dihydroartemisinin-piperaquine treated group.
Secondary outcome [1] 373641 0
The proportion of patients with treatment success ( an adequate clinical and parasitological response as indicators of efficacy) .or treatment failure ( early treatment failure, late clinical failure, late parasitological failure) applying WHO definition as follow;
Early treatment failure
• danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia;
• parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature;
• parasitaemia on day 3 with axillary temperature greater than or equal to 37.5 ºC;
• parasitaemia on day 3 equal to or more than 25% of count on day 0.
Late treatment failure
Late clinical failure
• danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (day 42) in patients who did not previously meet any of the criteria of early treatment failure;
• presence of parasitaemia on any day between day 4 and day 28 with axillary temperature equal to or more than 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure
Late parasitological failure
• presence of parasitaemia on any day between day 7 and day 28 (day 42) with axillary temperature less than 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure
Adequate clinical and parasitological response
• absence of parasitaemia on day 28(day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure
Timepoint [1] 373641 0
After 28 day follow up in artemether-lumifantrine treated group , or after 42 day follow up in dihydroartemisinin-piperaquine treated group.

Eligibility
Key inclusion criteria
mono-infection with P. falciparum detected by microscopy (parasitaemia of 500-100,000/µl asexual forms) or P. vivax detected by microscopy (parasitaemia more than equal to 250/µl asexual forms), or• presence of axillary temperature moret than or equal to 37.5 °C or history of fever during the past 24 hr, or ability to swallow oral medication, or ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule, or informed consent from the patient or from a parent or guardian in the case of children aged less than age of majority, informed assent from any minor participant aged from 12 to age of majority years, and consent for pregnancy testing from female of child-bearing age (defined as age greater than 12 years and sexually active) and from their parent or guardian if under the age of majority years.
Minimum age
6 Months
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
presence of signs of severe falciparum malaria according to the definitions of WHO,, female aged from 12 years and age of majority, weight under 5 kg, haemoglobin less than 8 g/dl, 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 less than 110 mm,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), Female patients who are sexually active within the age range of 12-17 year will be excluded, 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); and a positive pregnancy test or breastfeeding, unable to or unwilling to take a pregnancy test or contraceptive (for 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
None
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The SPSS software program will be used for data management and analysis. Data will be analyzed using two methods: the per protocol analysis, where patients who are withdrawn from the study or who are lost to follow-up will not be included, and the survival analysis, in which all enrolled patients (including those who were withdrawn from the study or who were lost to follow-up) will be included in the analysis until the last day before drop-out.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/01/2020
Actual
Date of last participant enrolment
Anticipated
31/07/2020
Actual
Date of last data collection
Anticipated
31/10/2020
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment outside Australia
Country [1] 21752 0
Myanmar
State/province [1] 21752 0
Rakhine State

Funding & Sponsors
Funding source category [1] 303510 0
Government body
Name [1] 303510 0
Ministry of Health and Sports
Country [1] 303510 0
Myanmar
Primary sponsor type
Government body
Name
Ministry of Health and Sports
Address
Office number (4), Zaya HtaNy Road, Ministry Zone, Pobba Thiri , Nay Pyi Taw, 15011,
Country
Myanmar
Secondary sponsor category [1] 303590 0
None
Name [1] 303590 0
None
Address [1] 303590 0
Country [1] 303590 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304035 0
Ethics Review Committee, Department of Medical Research, Ministry of Health and Sports, Myanmar
Ethics committee address [1] 304035 0
No. 5, Ziwaka Road, Dagon Township, Yangon 11191
Ethics committee country [1] 304035 0
Myanmar
Date submitted for ethics approval [1] 304035 0
08/07/2019
Approval date [1] 304035 0
Ethics approval number [1] 304035 0

Summary
Brief summary
Purpose of the study is to determine efficacy and safety of artemether -lumefantrine, and dihydroartemisinine-pipraquine for the treatment of uncomplicated Plasmodium falciparum malaria and chloroquine for Plasmodium vivax in Buthitaung, Rakhine state, Myanmar. The study will be conducted during October 2019 to September 2020. Total 150 patients will be enrolled (, 50 falciparum malaria cases for artemether-lumefantrine trial, 50 falciparum malaria cases for dihyddroartemisinin-piperaquine trial and 50 vivax malaria cases for chloroquine trial.
Clinical and parasitological parameters will be monitored over 28-days follow-up period for artemether-lumefantrine trial and chloroquine trial group, and 42 days for dihyddroartemisinin-piperaquine trial group to evaluate drug efficacy and safety
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95614 0
Dr KAY THWE HAN
Address 95614 0
Department of Medical Research
No.5, Ziwaka Road, Dagon Township, Yangon 11191
Country 95614 0
Myanmar
Phone 95614 0
+95 9 5169228
Fax 95614 0
+95 1 251514
Email 95614 0
drkaythwehan@yahoo.com
Contact person for public queries
Name 95615 0
Dr KAY THWE HAN
Address 95615 0
Department of Medical Research
No.5, Ziwaka Road, Dagon Township, Yangon 11191
Country 95615 0
Myanmar
Phone 95615 0
+95 9 5169228
Fax 95615 0
+95 1 251514
Email 95615 0
drkaythwehan@yahoo.com
Contact person for scientific queries
Name 95616 0
Dr Pascal Ringwald
Address 95616 0
Global Malaria Programme
World Health Organization
20 Avenue Appia
1211 Geneva 27
Switzerland
Country 95616 0
Switzerland
Phone 95616 0
+41 22 791 2533
Fax 95616 0
+41 22 791 4824
Email 95616 0
ringwaldp@who.int

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We have committed to keep these data confidentially since we ask for consent.


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.