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Trial registered on ANZCTR


Registration number
ACTRN12621001743853
Ethics application status
Approved
Date submitted
11/05/2021
Date registered
20/12/2021
Date last updated
20/12/2021
Date data sharing statement initially provided
20/12/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated Plasmodium falciparum malaria and chloroquine for the treatment of uncomplicated Plasmodium vivax malaria in Binh Phuoc, Gia Lai and Phu Yen provinces, Viet Nam in 2021.
Scientific title
Efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated Plasmodium falciparum malaria and chloroquine for the treatment of uncomplicated Plasmodium vivax malaria in Binh Phuoc, Gia Lai and Phu Yen provinces, Viet Nam in 2021.
Secondary ID [1] 304208 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients infected Plasmodium falciparum 321900 0
Patients infected Plasmodium vivax 321901 0
Condition category
Condition code
Infection 319627 319627 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For the treatment of uncomplicated P. falciparum malaria:
Artesunate-pyronaridine (Pyramax®, Shin Poong Pharmaceuticals). One tablet contains 60mg artesunate+ 180mg pyronaridine. Dosing will be according to body weight
Pyronaridine-artesunate will be taken orally with water, once daily for 3 days. Each dose will be administered under supervision in the clinic or if not possible by a home visitor to the patient’s home. A dose will be repeated in full if vomiting occurs within 30 minutes of administration of the first day of administration only.
Weight: 20-<24kg, Daily dose:PYR 180mg+AS 60mg, Number of tablets: 1
Weight: 24-<45kg, Daily dose:PYR 360mg+AS 120mg, Number of tablets: 2
Weight: 45-<65kg, Daily dose:PYR 540mg+AS 180mg, Number of tablets: 3
Weight: >65kg, Daily dose: PYR 720mg+AS 240mg, Number of tablets: 4


For the treatment of P. vivax malaria:
- Chloroquine tablets containing 150 mg of chloroquine base, all patients will be received a full treatment dose of 25 mg of chloroquine base per kg given over 3 days
D1 : 10 mg per kgbw
D2 : 10 mg per kgbw
D3 : 5 mg per kgbw
Intervention code [1] 320543 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327488 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.
All of the above outcomes are indicators for one goal, the goal of evaluating the effectiveness of the research drug
- Early treatment failure when the patient has 1 of the following symptoms:
+Development of danger signs or severe malaria on days D1, D2 or D3, with presence of malaria parasites.
+Density of malaria parasites on day D2 is higher than on day Do, even if the patient has no fever.
+Remaining parasites on day D3 and armpit temperature 37.5 C.
+Parasite density on day D3 25% of parasite density on day D0.
-late clinical failure: The patient reappeared with fever from day 4 (D4) to day 42 (D42) after treatment.
-late parasitological failure: Patients have malaria parasites from day 4 (D4) to day 42 (D42) after treatment.
-An adequate clinical and parasitological response: The patient had no clinical symptoms and was free of malaria parasites after 3 days of treatment (D3) and did not have malaria parasites during the follow-up period up to day D42.
Timepoint [1] 327488 0
Evaluate weekly for 42 days after dose.
Patients are monitored clinically and blood parasites from day 0, day 1, day 2, day 3, day 7, day 14, day 21, day 28, day 35 and day 42 (primary endpoint) from the start of taking the drug
Primary outcome [2] 327489 0
To evaluate the frequency and nature of adverse events after dose by questionnaire, observation, clinical examination, participant self-reported. Potential adverse events include headache, dizziness, insomnia, vomit, nausea, stomachache, diarrhea and rashes.
Timepoint [2] 327489 0
Assess after doses at D1, D2, D3, D7, D14, D21 and D28
Primary outcome [3] 329738 0
Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis for P. falciparum only.
Timepoint [3] 329738 0
patient reappeared P. falciparum parasite before D42
Secondary outcome [1] 395328 0
The number of patients positive for malaria on blood slide at 72 hours after treatment initiation
Timepoint [1] 395328 0
Assess every 24 hours for 72 hours after first dose by taken blood slides then stain with giemsa and exam by microscopy ( microccopic blood examination) to detect malaria parasites
Secondary outcome [2] 395329 0
To determine the Parasite clearance time by microscopic blood examination.
Timepoint [2] 395329 0
Every 24 hours to negative slides
Secondary outcome [3] 395330 0
To determine the fever clearance time by themometer with axillary temperarute
Timepoint [3] 395330 0
Every 24 hours up to fall below 37.5 0C and remain there for at least 24 hours
Secondary outcome [4] 395331 0
Kaplan Meier analysis over 42 days for recrudescences and reinfections.
To evaluate relapse or re-infection we use blood drops on absorbent paper as PCR technique to determine.
Timepoint [4] 395331 0
Assess weekly for 42 days after doses

Eligibility
Key inclusion criteria
To assess the therapeutic efficacy and safety of artesunate-pyronaridine
• age between 07 to 60 ages;
• mono-infection with P. falciparum detected by microscopy;
• parasitaemia of 500 – 100,000/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.
• 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) and from their parent or guardian if under the age of majority years (18 years old).
To assess the therapeutic efficacy and safety of chloroquine
• age between 02 to 60 ages;
• mono-infection with P. vivax detected by microscopy;
• parasitaemia of 250 /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;
• 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.
Minimum age
2 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• presence of severe malaria according to the definitions of WHO ;
• weight under 20 kg with P. falciparum patients;
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• 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;
• 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 and who are sexually active.
• history of hypersensitivity reactions or contraindications to the medicine(s) being tested; and
• Unmarried female age 12 – 18 years old.

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 EPI-INFO 6.0 software from USA and Excelsheet program will be used for data management and analysis. Data will be analysed by two methods: the Kaplan-Meier method and per-protocol analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/10/2021
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
14/02/2022
Actual
Sample size
Target
42
Accrual to date
30
Final
Recruitment outside Australia
Country [1] 23700 0
Viet Nam
State/province [1] 23700 0
Binh Phuoc
Country [2] 24137 0
Viet Nam
State/province [2] 24137 0
Gia Lai
Country [3] 24138 0
Viet Nam
State/province [3] 24138 0
Phu Yen

Funding & Sponsors
Funding source category [1] 308581 0
Other
Name [1] 308581 0
World Health Organization
Country [1] 308581 0
Switzerland
Funding source category [2] 308582 0
Government body
Name [2] 308582 0
National Malaria control program
Country [2] 308582 0
Viet Nam
Primary sponsor type
Other
Name
World Health Organization
Address
Avenue Appia 20
CH-1211 Geneva 27,
Country
Switzerland
Secondary sponsor category [1] 309439 0
Government body
Name [1] 309439 0
National Malaria control Program
Address [1] 309439 0
34 Trung van, South Tu Liem, Ha Noi
Country [1] 309439 0
Viet Nam

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308521 0
Ethics Committee for Health Research of WHO regional office, Western Pacific Region.
Ethics committee address [1] 308521 0
United Nations Ave. Ermita, Manila, 1000 Metro Manila
Ethics committee country [1] 308521 0
Philippines
Date submitted for ethics approval [1] 308521 0
11/05/2021
Approval date [1] 308521 0
12/05/2021
Ethics approval number [1] 308521 0

Summary
Brief summary
The guidelines for malaria diagnosis and treatment in Vietnam was revised and issued in June 2020. Malaria diagnois and treatment are being provided free of charge in Vietnam. First line treatment of falciparum malaria is dihydroartemisinin-piperaquine (DHA-PIP) or artesunate-pyronaridine.We here propose an open-labelled clinical trial to assess the efficacy and safety of artesunate -pyronaridine for the treatment of uncomplicated falciparum malaria in Binh Phuoc, Gia Lai and Phu Yen in Viet Nam, where were confirmed dihydroartemisinin - piperaquine resistance
Interventional study for the assessment of drug efficacy and safety over 42 days Patients with acute uncomplicated P. falciparum malaria. Samples size: 42 patients.
One tablet contains 60 mg of artesunate and 180 mg of pyronaridine 3-day regimen Dosing will be according to body weight. All patients will have a blood smear examined every 24 hours from D0 – D3 or during the first week by microscopy until parasite clearance.
The primary endpoint of the study is day 42 PCR corrected ACPR ( Adequate clinical and parasitological response).
The secondary endpoints
• The numbers of patients with a positive malaria slide 72 hours after treatment initiation
• Fever clearance time and parasite clearance time.
• Kaplan Meier analysis over 42 days for recrudescence and reinfections.
• Documented AEs and SAEs and relationships to study drugs.
P. vivax-infected patients will be given Chloroquine for 3 days and monitored clinically and parasitically for 28 days after taking the drug.
Chloroquine tablets containing 150 mg of chloroquine base, all patients will be received a full treatment dose of 25 mg of chloroquine base per kg given over 3 days. Primaquine will be given after Day 28.
Chloroquine tablets are made in Vietnam.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110998 0
A/Prof Bui Quang Phuc
Address 110998 0
National Institute of Malariology, Parasitology and Entomology
245 Luong The Vinh str, Nam Tu Liem district, Hanoi city
Country 110998 0
Viet Nam
Phone 110998 0
+84913522874
Fax 110998 0
+842438540099
Email 110998 0
[email protected]
Contact person for public queries
Name 110999 0
A/Prof Tran Thanh Duong
Address 110999 0
Director of National Institute of Malriology, Parasitology and Entomology
24 Trung Van, South Tu Liem, Hanoi
Country 110999 0
Viet Nam
Phone 110999 0
+84916895919
Fax 110999 0
+84 24 38544326
Email 110999 0
[email protected]
Contact person for scientific queries
Name 111000 0
Dr Nguyen Van Hong
Address 111000 0
National Institute of Malariology, Parasitology and Entomology
245 Luong The Vinh str, Nam Tu Liem district, Hanoi city
Country 111000 0
Viet Nam
Phone 111000 0
+84368188919
Fax 111000 0
Email 111000 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


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.