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Trial registered on ANZCTR


Registration number
ACTRN12618001348246
Ethics application status
Approved
Date submitted
2/08/2018
Date registered
9/08/2018
Date last updated
9/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the efficacy and safety of the drugs Pyronaridine-Artesunate (Pyramax™) and Primaquine to treat uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Salavanh province, Lao PDR
Scientific title
Evaluation of the efficacy and safety of Pyronaridine-Artesunate (Pyramax™) with low-dose Primaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Salavanh province, Lao PDR
Secondary ID [1] 295733 0
Nil known
Universal Trial Number (UTN)
U1111-1218-5114
Trial acronym
TES (Therapeutic Efficacy Study )
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Malaria 309131 0
Condition category
Condition code
Infection 308011 308011 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All P.f & P.v partients will receive artesunate and pyronaridine.
One oral tablet of the drug contains 60mg artesunate+ 180mg pyronaridine. Drug will be given under supervised treatment according to the following dose based on body weight:
20kg to less than 24 kg = 1 tablet daily for 3 days
24 kg to less than 45 kg = 2 tablets daily for 3 days
45 kg to less than 65 kg = 3 tablets daily for 3 days
Equal or more than 65 kg = 4 tablets daily for 3 days
Oral Primaquine tablet will be administered as a single 15-mg adult dose (0.25 mg base/kg) for P. falciparum cases, and once daily (0.25 base/kg) for 14 days for G6PD normal P. vivax cases.
Intervention code [1] 312053 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306998 0
To assess the efficacy of pyronaridine-artesunate (PAS) with low dose primaquine.
test use blood smear for microscopy and dry blood spot for PCR
Timepoint [1] 306998 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.”
Primary outcome [2] 306999 0
Differentiate recrudescence from new infection in case of failure
assessment with PCR of blood samples from dried blood spot on filter paper
Timepoint [2] 306999 0
Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) of the dried blood spot at time of recurrent infection or failure anytime between Day 3 to Day 42.
Secondary outcome [1] 350315 0
Safety, by evaluating the incidence of adverse events (example: vomiting, abdominal pain, rashes) by clinical observation of symptoms
Timepoint [1] 350315 0
Daily assessments from Day 0 to Day 7.

Eligibility
Key inclusion criteria
- Adults and children more than or equal to 7 years old and more than or equal to 20 kg body weight except unmarried females between 12 and 18 years old (potential unpredicted pregnancy);
- Slide-confirmed mono-infection with P. falciparum or P. vivax;
- 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 equal to or more than 37.5 °C or history of fever during the past 24 hours
- ability to swallow by mouth 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 adult patients, and from a parent or guardian in the case of children aged less than 18 years;
- informed assent from any minor participant aged 12 to 18 years; and
- consent for pregnancy testing from female of child-bearing potential and from their parent or guardian if under 18 years.
Minimum age
7 Years
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 or vivax malaria according to the definitions of WHO ;
- Children less than 7 years old and less than 20 kg body weight
- 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 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;
- unable to or unwilling to take a pregnancy test or unwilling to take pregnancy test or contraceptives (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)
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 treatment failure rate to Pyronaridine-Artesunate in the area is unknown, 10% has been chosen. At a confidence level of 95% and a precision around the estimate of 8%, a minimum of 50 patients 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 for P. falciparum and 60 patients for P.vivax .

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] 20725 0
Lao People's Democratic Republic
State/province [1] 20725 0
Salavanh Province

Funding & Sponsors
Funding source category [1] 300322 0
Other
Name [1] 300322 0
World Health Oranization
Country [1] 300322 0
Lao People's Democratic Republic
Funding source category [2] 300323 0
Government body
Name [2] 300323 0
Ministry of Health
Country [2] 300323 0
Lao People's Democratic Republic
Primary sponsor type
Government body
Name
Ministry of Health
Address
Samsenthai Road, Ban Thatkhao, Sisattanack District
Vientiane Capital
Country
Lao People's Democratic Republic
Secondary sponsor category [1] 299760 0
None
Name [1] 299760 0
Address [1] 299760 0
Country [1] 299760 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301134 0
National Ethics Committee for Health Research
Ethics committee address [1] 301134 0
SamsenThai Road, Kanyot village, Sisathanat district, Vientiane capital
Ethics committee country [1] 301134 0
Lao People's Democratic Republic
Date submitted for ethics approval [1] 301134 0
02/05/2018
Approval date [1] 301134 0
20/06/2018
Ethics approval number [1] 301134 0
062/NECHR
Ethics committee name [2] 301135 0
WHO Ethics Research Committee
Ethics committee address [2] 301135 0
WHO Western Pacific Regional Office, UN Avenue, Manila
Ethics committee country [2] 301135 0
Philippines
Date submitted for ethics approval [2] 301135 0
26/06/2018
Approval date [2] 301135 0
25/07/2018
Ethics approval number [2] 301135 0
2018.8.LAO.3.MVP

Summary
Brief summary
This study is an open prospective evaluation of clinical and parasitological responses to directly observed treatment of patients with uncomplicated falciparum and vivax malaria who meet the study inclusion criteria. They will be treated on site with pyronaridine-artesunate, and monitored for 42 days for falciparum and 28 days for vivax. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. With 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 a true recrudescence due to treatment failure and episodes of reinfection for uncomplicated P. falciparum and P. vivax malaria.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2939 2939 0 0
/AnzctrAttachments/375729-Ethical approval.pdf (Ethics approval)

Contacts
Principal investigator
Name 85974 0
Dr Bouasy Hongvanthong
Address 85974 0
Center of Malariology, Parasitology and Entomology
Nongdouang road, Ban Khoualuang Tai , Chanthabouly district, Vientiane Capital
Country 85974 0
Lao People's Democratic Republic
Phone 85974 0
+856 21 214040
Fax 85974 0
+ 856 21 218131
Email 85974 0
[email protected]
Contact person for public queries
Name 85975 0
Vienxay Vanisaveth
Address 85975 0
Center of Malariology, Parasitology and Entomology
Nongdouang road, Ban Khoualuang Tai , Chanthabouly district, Vientiane Capital
Country 85975 0
Lao People's Democratic Republic
Phone 85975 0
+ 856 21 214040
Fax 85975 0
+ 856 21 218131
Email 85975 0
[email protected]
Contact person for scientific queries
Name 85976 0
Pascal Ringwald
Address 85976 0
World Health Organization, 20 Av, Appia, 1211 Geneva 27
Country 85976 0
Switzerland
Phone 85976 0
+41227913469
Fax 85976 0
+41227914824
Email 85976 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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