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Trial registered on ANZCTR


Registration number
ACTRN12621000100897
Ethics application status
Approved
Date submitted
28/10/2020
Date registered
1/02/2021
Date last updated
1/02/2021
Date data sharing statement initially provided
1/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical trial to evaluate the effectiveness and safety of Nao Xin Qing (NXQ), a standardised herbal medicine in patients with ischaemic Stroke.
Scientific title
A Randomised, Double-Blind, Placebo Controlled Trial to Evaluate the Effectiveness and Safety of Nao Xin Qing (NXQ), a Standardised Herbal Medicine in Patients with Ischaemic Stroke.
Secondary ID [1] 302639 0
Trial protocol number: NXQIS01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 319537 0
Condition category
Condition code
Stroke 317488 317488 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be conducted as a two-arm randomized, double-blind, placebo controlled clinical trial of 36 weeks, including a 12-week intervention and 26-week follow-up.

For a two-arm trial, participants will be randomized after informed consent is obtained, into two parallel treatment groups:
a. Intervention group taking NXQ (Active)
b. Placebo control group (Placebo)

Intervention
Active NXQ 0.41g tablet, composition:
• Diospyros Kaki leaf extract 50 mg (active component)
• Starch
• Sucrose Powder
• Magnesium stearate
• Microcrystalline cellulose
Participants in Group 1 will take 3 NXQ tablets, three times per day for 12 weeks.

At each appointment, an allocation of medication will be dispensed to participants by research personnel according to the pre-coded container labelling. Participants will be required to return the original containers and any unused medication for monitoring and adherence to the intervention. Any unused medication will then be destroyed locally with approval of the coordinating chief investigator. All delivered and dispensed, unused and returned quantities will be recorded in a medication log.
Intervention code [1] 318932 0
Treatment: Other
Comparator / control treatment
Placebo
Placebos will be created by the same manufacturer to have similar colour, taste, texture and weight and will have no constituents which provide therapeutic effects. Participants in Group 2 will take 3 placebo tablets, three times per day for 12 weeks.

Placebo 0.41g tablet, composition:
starch
Sucrose
Magnesium stearate
Microcrystalline Cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 325527 0
NIHSS
The National Institutes of Health Stroke Scale (NIHSS) is a graded neurological examination rating speech and language, cognition, visual field deficits, motor and sensory impairments, and ataxia, which has become a standard part of the clinical assessments used in many recent interventional trials.
Timepoint [1] 325527 0
Baseline/pre-intervention (Wk0), midpoint (Wk6), primary timepoint (Wk12), follow-up (Wk18).
Primary outcome [2] 325528 0
mRS
The modified Rankin scale (mRS) commonly used scale, which measures the degree of disability or dependence in the daily activities of individuals who have suffered a stroke or other neurological disability.

The mRS is being used to measure the degree of dependence on others.
Timepoint [2] 325528 0
Baseline/pre-intervention (Wk0), midpoint (Wk6), primary timepoint (Wk12), follow-up (Wk18).
Secondary outcome [1] 388288 0
SSQOL
The Stroke-Specific Quality of Life Scale (SSQOL) is a self-report questionnaire which consists of 49 items across the 12 domains of assessment including: energy, family roles, language, mobility, mood, personality, self-care, social roles, thinking, upper extremity function, vision, and work/productivity
Timepoint [1] 388288 0
Baseline/pre-intervention (Wk0), midpoint (Wk6), secondary timepoint (Wk12), follow-up (Wk18)
Secondary outcome [2] 388289 0
Barthel Scale
Barthel Scale, also known as the Barthel ADL Index, a widely used ordinal scale measuring performance in activities of daily living including feeding, bathing, grooming, dressing, toilet use, mobility and stairs
Timepoint [2] 388289 0
Baseline/pre-intervention (Wk0), midpoint (Wk6), secondary timepoint (Wk12), follow-up (Wk18)
Secondary outcome [3] 388290 0
Safety assessed via composite of hemorheology, coagulation index, lipid profile, inflammatory markers, liver and renal function test

Patients will be sent to a Laverty Pathology laboratory for blood sampling and pathology testing. The assessment of lipid profiles will include triglycerides, total serum cholesterol, high density lipoprotein cholesterol and low-density lipoprotein cholesterol. The assessment of inflammatory markers will include tumour necrosis factor alpha and c-reactive protein.
Timepoint [3] 388290 0
Baseline/pre-intervention (Wk0), safety and tolerance visit (Wk2), midpoint (Wk6), secondary timepoint (Wk12), follow-up (Wk18)
Secondary outcome [4] 388291 0
Montreal Cognitive Assessment (MoCA)

The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting mild cognitive impairment (MCI) as currently conceptualized in patients performing in the normal range on the Mini-Mental State Examination. The MoCA provides an overall score based on the following domains: short-term memory recall task, visuospatial abilities, executive function, attention, concentration, working memory, language, and orientation to time and place.
Timepoint [4] 388291 0
Baseline, pre-intervention (Wk0), midpoint (Wk6), secondary timepoint (Wk12)

Eligibility
Key inclusion criteria
To participate in this study, participants must:
• Be between the ages of 40-80 years;
• Be an outpatient diagnosed with atherosclerotic ischaemic stroke;
• Have suffered from a stroke no less than 2 weeks and no more than 3 months at screening;
• Have an NIHSS score equal or greater than 5 scores and equal or less than 25 scores;
• Have a premorbid Modified Rankin Scale (mRS) score between 0 and 2;
• Agree to take part in the study as evidenced by a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative if the subject is unable to provide consent), has been informed of all pertinent aspects of the study;
• Ability to read and communicate in the English language.
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from this study if they have any of the following:
• Cerebral haemorrhagic stroke.
• Clinical assessment concluding the cause of ischaemic stroke from brain tumour, trauma, metabolic disorders, rheumatic valvular heart disease, and infectious cause of stroke.
• Participant has non-valvular atrial fibrillation.
• Concomitant clinical conditions affecting neural and motor function assessment including pre-existing dementia, inflammatory or non-inflammatory arthropathies or other medical disorders that result in a premorbid mRS of 3 or greater.
• Abnormal pathology test results: Cr > 1.5 times upper limit of normal (ULN); ALT, AST or ALP > 2 times ULN; PT > 3 second more than ULN; APTT > 10 seconds more than ULN; Plt < 100,000/mcL;
• Patients with severe depression or other psychiatric disorders that have not been stabilised for > 3 months prior to randomisation.
• Known allergy to the medication ingredients.
• Participant of another clinical trial within the past 3 months.
• Consuming D. Kaki L extract.
• Participant requires combination of dual antiplatelet therapy, for example, aspirin and clopidogrel with the exception of aspirin and dipyridample.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be conducted external to the primary research team by a research officer of NICM Health Research Institute. This person will be responsible for producing computer generated randomisation treatment sequences, which randomly associate a randomisation number with either active or placebo treatment. NICM’s Clinical Trials Manager and Strategic Operations Manager are responsible for securely storing the randomisation allocation in a restricted access electronic file.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation numbers will be allocated in permuted blocks of 4 randomisation numbers starting from 01 to 88 with each block containing 2 active and 2 placebo assigned randomisation numbers. Sites will allocate the randomisation numbers in order of number sequence starting with the lowest number in each block and using all numbers in a block of 4 before starting with the next block of numbers. As soon as the randomisation number is assigned, it will be recorded on the screening log, in the participant source data file and electronic Case Report Form (eCRF). Details of any participants randomised out of sequence will be notified immediately to the Coordinating chief investigator.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Thirty-seven participants per group provide 80% power to detect a detect a 2 unit difference in mean NIHSS score between treatment and control groups at follow-up, at the 0.05 significance level using a 2-sided independent samples test t-test and assuming a standard deviation of 3 units (G-Power software, University of Trier, Trier, Germany). A 2-unit improvement in mean NIHSS score represents a non-controversial improvement, which has the potential to lead to changes in clinical care (despite any additional cost and/or pill load). The target sample size will therefore be 88 participants in total, 44 per group, which includes 20% dropout boundary.

Primary efficacy analysis
The primary analysis will be linear mixed models through which we will test for differences between treatment groups on each outcome over time, with adjustment for random variation between treatment centres, with and without adjustment for other potentially important predicts (e.g. compliance, age, and gender). The random effects are at both the patient and site level. Non-linear changes over time will be tested by a) fitting time as categorical variable and b) testing for quadratic and cubic effects. Results will be reported as regression coefficients (or odds ratios if categorical) and associated 95% confidence intervals.

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 in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17905 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 17906 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [3] 17907 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 31766 0
2170 - Liverpool
Recruitment postcode(s) [2] 31767 0
2200 - Bankstown
Recruitment postcode(s) [3] 31768 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 307075 0
University
Name [1] 307075 0
Western Sydney University
Address [1] 307075 0
Western Sydney University
Locked Bag 1797, Penrith, NSW, 2751
Country [1] 307075 0
Australia
Funding source category [2] 307076 0
Commercial sector/Industry
Name [2] 307076 0
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd.
Address [2] 307076 0
No. 389, Shatai North Road,
Baiyun District, Guangzhou Guangdong 510515
Country [2] 307076 0
China
Primary sponsor type
University
Name
Western Sydney University
Address
Western Sydney University
Locked Bag 1797, Penrith, NSW, 2751
Country
Australia
Secondary sponsor category [1] 307643 0
None
Name [1] 307643 0
Address [1] 307643 0
Country [1] 307643 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307194 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 307194 0
Research Directorate
Locked Bag 7103
LIVERPOOL BC NSW 1871
Ethics committee country [1] 307194 0
Australia
Date submitted for ethics approval [1] 307194 0
01/05/2020
Approval date [1] 307194 0
29/09/2020
Ethics approval number [1] 307194 0
2020/ETH01046

Summary
Brief summary
Stroke is the third leading cause of death in Australia. Ischaemic stroke accounts for ~80% of all stroke cases and is caused by a narrowing or obstruction of the blood vessels resulting in oxygen and nutrient deprivation. Conventional post-stroke management involves combining pharmacotherapy and rehabilitative therapies.
Nao Xin Qing (NXQ) is a TGA-approved product (AUSTL196297) in Australia. NXQ is a novel herbal formula made from the standardised extract of persimmon leaves. NXQ has been used clinically in China for numerous years in the treatment of apoplexy, coronary heart disease and enhance recovery from ischemic stroke.
The aim of this randomised double-blind controlled study is to assess the clinical effectiveness of NXQ for ischaemic stroke patients during rehabilitation phase. This will provide preliminary data whether NXQ can be used as an effective treatment of ischaemic stroke recovery, to prevent recurrence of stroke and improve quality of life of stroke survivors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106358 0
Prof Dennis Cordato
Address 106358 0
Neurophysiology Department
Clinic 111, Level 1, Clinical Services Building, Liverpool Hospital,
Liverpool, NSW, 2170
Country 106358 0
Australia
Phone 106358 0
+61287383646
Fax 106358 0
Email 106358 0
Dennis.Cordato@health.nsw.gov.au
Contact person for public queries
Name 106359 0
Dr Angelo Sabag
Address 106359 0
NICM Health Research Institute Western Sydney University,
Locked Bag 1797, Penrith, NSW, 2751, Australia
Country 106359 0
Australia
Phone 106359 0
+61410232582
Fax 106359 0
+61296854760
Email 106359 0
a.sabag@westernsydney.edu.au
Contact person for scientific queries
Name 106360 0
Dr Angelo Sabag
Address 106360 0
NICM Health Research Institute Western Sydney University,
Locked Bag 1797, Penrith, NSW, 2751, Australia
Country 106360 0
Australia
Phone 106360 0
+61410232582
Fax 106360 0
+61 02 96854760
Email 106360 0
a.sabag@westernsydney.edu.au

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?
Study protocol
How or where can supporting documents be obtained?
Type [1] 9549 0
Study protocol
Citation [1] 9549 0
Link [1] 9549 0
Email [1] 9549 0
a.sabag@westernsydney.edu.au
Other [1] 9549 0
The study protocol has been uploaded to the ANZCTR portal at registration.
Summary results
No Results