Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618001349235
Ethics application status
Approved
Date submitted
3/08/2018
Date registered
9/08/2018
Date last updated
9/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluate the efficacy and safety of Artesunate-mefloquine (ASMQ) and low dose primaquine to treat uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Champasack province, Lao PDR
Scientific title
Efficacy and safety of Artesunate-mefloquine with low dose primaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Champasack province, Lao PDR
Secondary ID [1] 295734 0
None
Universal Trial Number (UTN)
Trial acronym
TES ( Therapeuty Efficacy Study )
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Malaria 309132 0
Condition category
Condition code
Infection 308012 308012 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One oral tablet for children contains 25 mg artesunate+ 55 mg Mefloquine (ASMQ), and for adults it contains 100 mg artesunate+ 220 mg Mefloquine. Drug will be administered under direct supervision according to body weight, once daily for 3 days for both P. vivax and P. falciparum.
For children:
5-8 kg one tablet daily for 3 days
9-17 kg two tablets daily for 3 days

For adults:
18-29 kg one tablet daily for 3 days
Equal to or more than 30 kg 2 tablets daily for 3 days

Oral primaquine will be administered under direct supervision as a single 15-mg adult dose (0.25 mg base/kg) on day 0 for P. falciparum cases only, and once daily (0.25 base/kg) for 14 days for G6PD defficient P. vivax participants.
Intervention code [1] 312055 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307000 0
Proportion of treatment success confirmed by using blood smears for microscopy and dry blood spot for Polymerase Chain-Reaction (PCR).
Timepoint [1] 307000 0
42 days after treatment is the primary timepoint. Patients will be assessed daily on Day 0, 1, 2 and 3, and weekly thereafter (D7, D14, D21, D28, D35) until Day 42.”
Secondary outcome [1] 350316 0
Evaluate safety by the incidence of adverse events assessed by clinical observation of symptoms. For example: vomiting, abdominal pain, and rashes.
Timepoint [1] 350316 0
Any time adverse events occur between Day 0 and Day 7.

Eligibility
Key inclusion criteria
- Age between aged between 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 to 100,000 per µl asexual forms;
- P. vivax parasitaemia of 250 to 60,000 per µl asexual forms
- Presence of axillary temperature equal or more then 37.5 °C or history of fever during the past 24 hours
- 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 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 more 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
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-presence of general danger signs in children aged under 12 years or 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 per dl
-mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition defined as a child aged between 6to 60 months whose weight-for-high is below –3 z-score
- 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);
- glucose-6-phosphate dehydrogenase deficiency for patient treated with 14 day primaquine;
- unmarried women 12 to 18 years old;
- a positive pregnancy test or breastfeeding; and
- unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age (defined as age more than 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)
None
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
None
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
As the Pf treatment failure rate to artemether-lumefantrine in the area is 0-10% (CMPE 2015), and unknown in P. vivax, and also unknown to ASMQ in both species, 90% has been chosen. At a confidence level of 95% and a precision around the estimate of 5%, a minimum of 50 patients for each species must be included. With a 20% increase to allow loss to follow-up and withdrawals during the 42-day follow-up period, 60 patients should be included in the study per malaria species and per drug tested

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/08/2018
Actual
Date of last participant enrolment
Anticipated
15/02/2019
Actual
Date of last data collection
Anticipated
29/03/2019
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment outside Australia
Country [1] 20726 0
Lao People's Democratic Republic
State/province [1] 20726 0
Champasack province

Funding & Sponsors
Funding source category [1] 300324 0
Other
Name [1] 300324 0
World Health Organization
Country [1] 300324 0
Lao People's Democratic Republic
Funding source category [2] 300325 0
Government body
Name [2] 300325 0
Ministry of Health
Country [2] 300325 0
Lao People's Democratic Republic
Primary sponsor type
Government body
Name
Ministry of Health
Address
Samsenthai road, Ban thatkhao, Sisattanak district, Vientiane Capital
Country
Lao People's Democratic Republic
Secondary sponsor category [1] 299762 0
None
Name [1] 299762 0
Address [1] 299762 0
Country [1] 299762 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301136 0
National Ethics Committee for Health Research
Ethics committee address [1] 301136 0
Samsenthai road, Ban kaoyot, sisattanak district,vientiane capital
Ethics committee country [1] 301136 0
Lao People's Democratic Republic
Date submitted for ethics approval [1] 301136 0
02/05/2018
Approval date [1] 301136 0
20/06/2018
Ethics approval number [1] 301136 0
061/NECHR
Ethics committee name [2] 301137 0
WHO Ethics Research Committee
Ethics committee address [2] 301137 0
WHO western Pacific Regional office , UN Avenue, Manila
Ethics committee country [2] 301137 0
Philippines
Date submitted for ethics approval [2] 301137 0
26/06/2018
Approval date [2] 301137 0
25/07/2018
Ethics approval number [2] 301137 0
2018.7.LAO.2.MVP

Summary
Brief summary
This study is an open 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 ASMQ and low dose primaquine for both Pf and Pv, and monitored for 42 days and 28 days for Pv. 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. PCR analysis will be used to distinguish between true recrudescence due to treatment failure and episodes of reinfection.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2940 2940 0 0
/AnzctrAttachments/375730-Ethics approval CPS.pdf (Ethics approval)

Contacts
Principal investigator
Name 85978 0
Dr Bouasy Hongvathong
Address 85978 0
Center of Malariology, Parasitology and Entomology
Nongdouang road, Ban khoualuang Tai, Chanthabouly district, vientian capital
Country 85978 0
Lao People's Democratic Republic
Phone 85978 0
+856 21 214040
Fax 85978 0
+ 856 21 218131
Email 85978 0
[email protected]
Contact person for public queries
Name 85979 0
Dr Viengxay Vanisaveth
Address 85979 0
Center of Malariology, Parasitology and Entomology
Nongdouang road, Ban khoualuang Tai, Chanthabouly district, vientian capital
Country 85979 0
Lao People's Democratic Republic
Phone 85979 0
+ 856 21 214040
Fax 85979 0
+ 856 21 218131
Email 85979 0
[email protected]
Contact person for scientific queries
Name 85980 0
Dr Pascal Ringwald
Address 85980 0
World Health Organization, 20 Av, Appia, 12211 Geneva 27
Country 85980 0
Switzerland
Phone 85980 0
+41227913469
Fax 85980 0
+41227914824
Email 85980 0
[email protected]

No information has been provided regarding IPD availability


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.