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Trial registered on ANZCTR


Registration number
ACTRN12619000937112
Ethics application status
Approved
Date submitted
12/06/2019
Date registered
5/07/2019
Date last updated
5/07/2019
Date data sharing statement initially provided
5/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of )a) Artemether-lumefantrine (b) Dihydroartemisinin piperaquine phosphate for the treatment of uncomplicated Plasmodium falciparum malaria in Tamu Township, Sagaing Region
Scientific title
Study on clinical and parasitological outcome of ACTs (a) Artemether-lumefantrine and (b) Dihydroartemisinin Piperaquine Phosphate for treatment of uncomplicated falciparum malaria in Tamu township, Sagaing Region
Secondary ID [1] 298424 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record
nil

Health condition
Health condition(s) or problem(s) studied:
malaria related fever 313155 0
headache 313156 0
malaise 313157 0
loss of appetite 313158 0
malaria 313159 0
Condition category
Condition code
Infection 311625 311625 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
a non-randomized coltrol trial will be used having two arms of treatment regimes. One arm will be given Artemether-Lumefantrine regime and another arm with Dihydroartemisinin Piperaquine Phosphate for uncomplicated falciparum malaria patients. All eligible patients for the study will be enrolled. The enrolled odd numbers will be Artemether-Lumefantrine while, the even numbers will be given Dihydroartemisinin Piperaquine Phosphate regime.
Each Artemether-Lumefantrine contains artemether 20 mg and lumefantrine 120 mg respectively. The drug will be given as:
(a) Body weight: 5-14 Kg. One tablet twice a day for three days
15-24 Kg. Two tablets twice a day for three days
25-34 Kg Three tablets twice a day for three days
35 Kg and above: Four tablets twice a day for three days
Each Tablet of Dihydroartemisinin Piperaquine Phosphate contains 40mg Dihydroartemisinin and 320 mg of Piperaquine Phosphate respectively
(a) Body weight: 5 to 9.9 Kg. 0,5 tablet once a day for three days
10- 19 Kg. One tablet once a day for three days
20-39 Kg Two tablets once a day for three days
40 Kg and above: Three tablets once a day for three days
All tablets will be given by oral administration
All the prescribed drugs will be given by the malaria staff of the township who will be recruited and trained as the member of the study team. The drugs will be administered to the patient by the malaria staff under direct observation. Also the emptied strips will be recollected by the study team.

Intervention code [1] 314676 0
Treatment: Drugs
Comparator / control treatment
Artemether- Lumefantrine regime will be regarded as a control regime
Control group
Active

Outcomes
Primary outcome [1] 320337 0
Adequate Clinical and Parasitological Response (ACPR) is a composite primary outcome
-Blood smears will be taken from clinically suspected malaria cases on Day 0,1,.2,3,7,14,21 and 28 days for Artemether-lumefantrein and 42 days for Dihydroartemisinin piperaquine phosphate regime.
Each follow up will consist of assessment of general condition, body temperature and microscopic examination of Giemsa Stained Thick smear
(Tympanic temperature will be assessed by using digital thermometer to a one decimal number)
(Malaria parasites will be identified and counted by two qualified laboratory technicians
If the difference of two readings are more than 10%, the third reader will be invited to confirm the results)
The study outcome will be classified as either (a) ACPR (Adequate Clinical and Parasitological Response) (b) Early Treatment Failure (ETF) or (c) Late Treatment Failure (LTF) depending on the cliinical and parasitological results
ACPR is the composite primary outcome.
It will indicate the efficacy of each regime as well as the safety of each treatment regime.
The outcome will assess:
(a) Therapeutic Efficacy
(b) Safety of treatment regarding the presence (or) absence of side effects in each visit so that the absence of side effects (or) Severe Adverse Effects (SAE) will indicate the safety of the regime. In each follow up visit, the research team member will ask the presence of any side effects: nausea, vomiting , diarrhoea, giddiness urticaria etc.
Timepoint [1] 320337 0
28 days from enrollment for Artemether-Lumefantrine and 42 days for Dihydroartemisinin piperaquine phosphate regime.
Day 0,1,2, and day 3 will be assessed on body temperature. parasite count and general conditions, to assess Early Treatment Failure (ETF)
Day 7,14,21,,28,35 and 42 will be assessed the same features for Late Treatment Failure (LTF).
Primary outcome [2] 320347 0
Early Treatment Failure (ETF)
If the patient has severe signs and symptoms of malaria within 3 days of treatment (or) fever present after three days of treatment ( tympanic temperature will be measured by digital thermometer to a one decimal point )
(or) malaria asexual parasites remain after three days of treatment)
(Malaria parasites will be identified and counted by two qualified laboratory technicians
If the difference of two readings are more than 10%, the third reader will be invited to confirm the results)
Timepoint [2] 320347 0
Three days after treatment
Secondary outcome [1] 371282 0
Late Treatment Failure (LTF)
It is assessed during 4-28 days of treatment by:
(a)General condition: Medical officer will perform clinical examination including level of consciousness,,inspection of pallor, measuring heart rate, respiration rate and blood pressure.
He will ask the patient if there was presence of vomiting, diarrhoea or other illness during this period.
(b) Body temperature ( tympanic temperature will be measured by digital thermometer to a one decimal point )

Timepoint [1] 371282 0
4-28 days after giving treatment.
Assessment will be done as a weekly basis: Day 7,14,21,and 28 for Artemether-Liumefantrine regime and additional 35 and 42 days for Dihydroartemisinin piperaquine phosphate regime.

Eligibility
Key inclusion criteria
Patients having fever with a parasitological count of 1000 asexual parasite count per 1 ul of blood for P falciparum malaria and 500 asexual parasite count per 1 ul of blood for P. vivax malaria
Minimum age
6 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients having severe and complicated malaria

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)
Allocation is not comcealed
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
Parallel
Other design features
P. falciparum malaria patients will be treated with either Artemether-lumefantrine (or) Dihydroartemisinin Piperaquine Phosphate regime
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Number of minimum patients needed to be recruited will be calculated according to the WHO Therapeutic Efficacy Studies Treatment Guidelines
Data obtained will be entered, cleared and analyzed according to the Standard Excel Template developed by WHO
The outcomes will be assessed by:
(a) Analysis of parasite counts and clinical conditions encountered in each visit can be classified for efficacy status
(b) Analysis of data on presence (or) absence of side effects in each visit will be classified for safety of the regime

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21596 0
Myanmar
State/province [1] 21596 0
Sagaing

Funding & Sponsors
Funding source category [1] 302965 0
Other Collaborative groups
Name [1] 302965 0
World Health Organization
Address [1] 302965 0
No. 4013 A, Shwe Taung Kyaw Street,
Bahan Township
Yangon Region
Myanmar
Country [1] 302965 0
Myanmar
Primary sponsor type
Other Collaborative groups
Name
World Health Organization
Address
No. 4013 A, Shwe Taung Kyaw Street,
Bahan Township
Yangon Region
Myanmar
Country
Myanmar
Secondary sponsor category [1] 302922 0
None
Name [1] 302922 0
nil
Address [1] 302922 0
nil
Country [1] 302922 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303519 0
Ethics Review Committee, Department of Medical Research
Ethics committee address [1] 303519 0
Department of Medical Research
No.(5) ZIwiKa Road, Dagon Township
Yangon Region, 11191
MYANMAR
Ethics committee country [1] 303519 0
Myanmar
Date submitted for ethics approval [1] 303519 0
04/04/2019
Approval date [1] 303519 0
14/05/2019
Ethics approval number [1] 303519 0
002716

Summary
Brief summary
The study will be done in Ta-mu township, Sagaing Region which is located in the norther-west part of the country along the Myanmar-India border.
It is regarded as the sentinel site by WHO to monitor the drug resistance malaria in the region as there is a lot of population migration along the two countries. The activity of monitoring the drug resistance malaria has been started since 2009 in this area.
The study is intended to start in July 2019 where clinically suspected malaria patients will be tested using Giemsa stained microscopic examination. Patients having asexual malaria parasites 1000 per micro-liter and above will be enrolled and given either artemether-lumefantrine or Dihydroartemisinin piperaquine phosphate which are the standard ACTs and regarded as standard regimes by the Ministry of Health and Sports. The patients will be followed up on days 2,3 and every week up to for 28 days for artemether-lumefantrine group (or) 42 days for those treated with Dihydroartemisinin piperaquine phosphate regime. The clinical symptoms will also be recorded during the visits and blood will be tested by microscopic examination as well as by filter papers for PCR test. Then findings will be classified as
(a) Adequate Clinical and Parasitological Repsonse (ACPR) (b) Early Treatment Failure or (c) Late Treatment Failure according to the WHO guidelines. The outcome will be assessed as efficacy of the regime.
(b) Presence (or) absence of side effects will be asked in each visit to assess the safety of each regime
Trial website
nil
Trial related presentations / publications
nil
Public notes
nil

Contacts
Principal investigator
Name 93946 0
Dr KHIN LIN
Address 93946 0
Department of Medical Research (Pyin Oo Lwin Branch), Ward No.(16) Pyin Oo Lwin Township,
Mandalay Region
MYANMAR
Country 93946 0
Myanmar
Phone 93946 0
095-0943151629
Fax 93946 0
095-8520-50251
Email 93946 0
dr.khinlin.dir@gmail.com
Contact person for public queries
Name 93947 0
Dr KHIN LIN
Address 93947 0
Department of Medical Research, Ward No.(16). Pyin Oo Lwin Township.
Mandalay Region
MYANMAR
Country 93947 0
Myanmar
Phone 93947 0
095-0943151627
Fax 93947 0
095-8520-50251
Email 93947 0
dr.khinlin.dir@gmail.com
Contact person for scientific queries
Name 93948 0
Dr KHIN LIN
Address 93948 0
Department of Medical Research (Pyin Oo Lwin Branch), Ward No.(16) Pyin Oo Lwin Township,
Mandalay Region
MYANMAR
Country 93948 0
Myanmar
Phone 93948 0
095-0943151629
Fax 93948 0
095-8520-50251
Email 93948 0
dr.khinlin.dir@gmail.com

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?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 2328 0
Ethical approval
Citation [1] 2328 0
Link [1] 2328 0
Email [1] 2328 0
Other [1] 2328 0
Summary results
No Results