Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001375943
Ethics application status
Approved
Date submitted
6/08/2019
Date registered
22/12/2020
Date last updated
22/12/2020
Date data sharing statement initially provided
22/12/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of artesunate-mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in Binh Phuoc and Dak Nong provinces, Viet Nam, in 2019.
Scientific title
Efficacy and safety of artesunate-mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in Binh Phuoc and Dak Nong provinces, Viet Nam, in 2019.
Secondary ID [1] 299607 0
None
Universal Trial Number (UTN)
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Patients infected Plasmodium falciparum malaria. 313952 0
Condition category
Condition code
Infection 312354 312354 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To assess the therapeutic efficacy of Artesunate-Mefloquine. The tablet for adults is 100 mg of artesunate and 200 mg of mefloquine; For Children, the tablet is 25 mg of artesunate and 50 mg of mefloquine.

The dose will be administered as a 3-day regimen, according to weight (kg) and age (year) as following:
. patients from 2 to under 5 years old, corresponding to weighing from 10 to less than 18 kg, taking 25mg / 50mg tablets, total 3 children tablets.
. patients from 5 to under 10 years old, corresponding to weight from 18 to less than 30 kg, take 100mg / 200mg tablets, total 3 adult tablets.
. patients over 10 years old, corresponding to weighing over 30 kg, taking 200mg / 400mg tablet, total 6 adult tablets.
Artesunate – mefloquine will be taken orally with water, once daily for 3 days. Each dose will be administered under supervision by health staff or if not possible monitored at the patient's home. A dose will be repeated in full if vomiting occurs within 30 minutes of administration of the first day. This event will be documented in the case record form (CRF).
Intervention code [1] 315234 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320985 0
The proportion of patient with an adequate clinical and parasitological response without and with PCR correction as indicators of treatment efficacy.
Clinical response and adequate parasite is upon: After 42 days of treatment with Artesunate-mefloquin since the first dose, the patient did not reappear plasmodium falciparum parasite in the blood and there was no fever
Timepoint [1] 320985 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 from the start of taking the drug .
Primary outcome [2] 321475 0
To evaluate the frequency and nature of adverse events after dose by questionnaire, obsevation, clinical examination, participant self-reported
Timepoint [2] 321475 0
Assess afer doses at D1, D2, D3, D7, D14, D21 and D28
Secondary outcome [1] 376083 0
The numbers of patients is the positive malaria slide at 72 hours after treatment initiation
Timepoint [1] 376083 0
Assess every 12 hours for 72 hours after dose by taken blood slides then stain with giemsa and exam by microscopy ( microccopic blood examination) to detect malaria parasites
Secondary outcome [2] 380336 0
To determine the Parasite clearance time by microscopic blood examination.
Timepoint [2] 380336 0
Every 12 hours to negative slides.
Secondary outcome [3] 380337 0
To determine the fever clearance time by themometer with axillary temparute
Timepoint [3] 380337 0
Every 12 hours up to fall below 37.5 0C and remain there for at least 24 hours
Secondary outcome [4] 380338 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] 380338 0
Assess weekly for 42 days after doses

Eligibility
Key inclusion criteria
• age between 02 to 60 ages;
• mono-infection with P. falciparum detected by microscopy;
• parasitaemia from 500 to 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 over 12 years and sexually active) and from their parent or guardian if under the age of majority years (18 years old).
Minimum age
2 Years
Maximum age
60 Years
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
• weight under 5 kg;
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• presence of severe malnutrition defined as a child aged 6-60 months whose weight-for-high is below –3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 115 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);
• 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)
None
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
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
Suspended
Date of first participant enrolment
Anticipated
Actual
30/10/2019
Date of last participant enrolment
Anticipated
25/12/2019
Actual
30/12/2019
Date of last data collection
Anticipated
21/02/2020
Actual
20/02/2020
Sample size
Target
84
Accrual to date
52
Final
Recruitment outside Australia
Country [1] 21751 0
Viet Nam
State/province [1] 21751 0
Binh Phuoc, Dak Nong

Funding & Sponsors
Funding source category [1] 303506 0
Other
Name [1] 303506 0
World Health Organization
Country [1] 303506 0
Switzerland
Funding source category [2] 303880 0
Government body
Name [2] 303880 0
National Malaria control programma
Country [2] 303880 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] 303559 0
Government body
Name [1] 303559 0
National Malaria control Program
Address [1] 303559 0
34 Trung van, South Tu Liem, Ha Noi
Country [1] 303559 0
Viet Nam

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304030 0
Ethics Committee for Health Research of WHO regional office, Western Pacific Region.
Ethics committee address [1] 304030 0
United Nations Ave. Ermita, Manila, 1000 Metro Manila
Ethics committee country [1] 304030 0
Philippines
Date submitted for ethics approval [1] 304030 0
08/03/2019
Approval date [1] 304030 0
18/03/2019
Ethics approval number [1] 304030 0
2019.15.VTN.2.MVP

Summary
Brief summary
Artesunate - Mefloquine is the most current efficacy of antimalarial drugs that has been used in some countries in Asia as Cambodia, Thailand…We here propose an open-labelled clinical trial to assess the efficacy and safety of artesunate - mefloquine for the treatment of uncomplicated falciparum malaria in Dak Nong, Binh Phuoc in Central and Southern 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: 84 patients.
One tablet contains 100mg of artesunate and 200mg of mefloquine or 25 mg of artesunate and 50 mg of mefloquine for childrens will be administered as a 3-day regimen Dosing will be according to body weight. All patients will have a blood smear examined every 12 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95598 0
A/Prof Bui Quang Phuc
Address 95598 0
National Institute of Malariology, Parasitology and Entomology
245 Luong The Vinh str, Nam Tu Liem district, Hanoi city
Country 95598 0
Viet Nam
Phone 95598 0
+84913522874
Fax 95598 0
+842438540099
Email 95598 0
[email protected]
Contact person for public queries
Name 95599 0
A/Prof Tran Thanh Duong
Address 95599 0
Director of National Institute of Malriology, Parasitology and Entomology
24 Trung Van, South Tu Liem, Hanoi
Country 95599 0
Viet Nam
Phone 95599 0
+84916895919
Fax 95599 0
+84 24 38544326
Email 95599 0
[email protected]
Contact person for scientific queries
Name 95600 0
A/Prof Ta Thi Tinh
Address 95600 0
National Institute of Malriology, Parasitology and Entomology
24 Trung Van, South Tu Liem, Hanoi
Country 95600 0
Viet Nam
Phone 95600 0
+84912484889
Fax 95600 0
Email 95600 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.