Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000388415
Ethics application status
Approved
Date submitted
9/03/2016
Date registered
24/03/2016
Date last updated
22/03/2022
Date data sharing statement initially provided
21/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-anginal Efficacy of Ticagrelor in Coronary Slow Flow.
Scientific title
Ticagrelor In Coronary microvascular dysfunction (TIC) Program: Anti-anginal Efficacy in Primary Coronary Microvascular Disorders.
Secondary ID [1] 288501 0
None
Universal Trial Number (UTN)
Trial acronym
TIC-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Slow Flow Phenomenon 297571 0
Condition category
Condition code
Cardiovascular 297767 297767 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral administration comprising the dose of 90mg Ticagrelor or Placebo twice daily for a total period of 8 weeks (4 weeks each) to assess the effect of ticagrelor on angina frequency in patients with Coronary Slow Flow who experience angina at least 3 times/week.

After the first 4 weeks (Phase 1) completed, two weeks washout period is allowed, patients will not need to take any study tablets specifically for this trial in the washout period.

The investigational product will be packed in bottle covering the period from one visit to the next. Each patient will receive and return the designated bottle at the regular site visits.
Intervention code [1] 293866 0
Treatment: Drugs
Comparator / control treatment
This study is designed as a double-­blind, placebo controlled, crossover study. Placebo drug will involve taking a drug (for 4 weeks) that looks similar in appearance to Ticagrelor but will not affect the patient in any way.

Placebo consists of lactose monohydrate, microcrystalline cellulose, and magnesium stearate. The composition of the film- coat is identical to that of the corresponding strength of ticagrelor active tablets.
Control group
Placebo

Outcomes
Primary outcome [1] 297295 0
To assess the effect of ticagrelor 90mg bd on angina frequency in patients with Coronary Slow Flow who experience angina at least 3 times/week.

Patients will maintain an angina diary throughout this study period. This diary will describe the frequency and characteristics of chest pain (i.e. the time of day, severity, triggers, etc.). In addition, we will administer Seattle Angina Questionnaire (SAQ) at screening and at the end of each phases.
Timepoint [1] 297295 0
Before the administration of any drug : For 2 weeks using the angina diary and SAQ
Medication phase 1 : For 4 weeks using the angina diary
At the end of Phase 1: SAQ
Washout period : For 2 weeks using the angina diary
Medication phase 2 (cross over) : For 4 weeks using the angina diary
At the end of Phase 2: SAQ
Secondary outcome [1] 320650 0
(i) Frequency of prolonged angina episodes (ie episodes persisting > 20 minutes)
- assessed from patient's self reported angina diary
Timepoint [1] 320650 0
Angina diary is completed every week and frequency compared as below.
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2
Secondary outcome [2] 321637 0
Sublingual nitrate consumption assessed by angina diary
Timepoint [2] 321637 0
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2
Secondary outcome [3] 321638 0
Angina frequency as assessed by Seattle Angina Questionnaire (SAQ)
Timepoint [3] 321638 0
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2
Secondary outcome [4] 321639 0
Physical health summary scores assessed by Short form 36
Timepoint [4] 321639 0
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2
Secondary outcome [5] 321640 0
Plasma adenosine levels will be measured by high-performance liquid chromatography
Timepoint [5] 321640 0
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2
Secondary outcome [6] 321645 0
Patient medication compliance assessed by asking each patient to return their product containers and a tablet count performed at each visit.
Timepoint [6] 321645 0
-End of Phase 1
-End of Phase 2
Secondary outcome [7] 322061 0
mental health summary scores assessed by Short form 36
Timepoint [7] 322061 0
-At baseline (Before the administration of the drug)
-End of Phase 1
-End of Phase 2

Eligibility
Key inclusion criteria
For inclusion in the study subjects should fulfill the following criteria:
I. Provision of informed consent prior to any study specific procedures
II. Female and/or male patients aged greater than or equal to 18 years
III. Documented angiographic features of coronary slow flow. as defined by TIMI-2 flow (i.e. requiring more than 3 beats to opacify a major epicardial vessel) in the absence of obstructive coronary artery disease (i.e. no epicardial lesion greater than 50%).
IV. Chest pain occurring more than or equal to 3 times/week in the preceding two weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
I. Acute coronary syndrome admission within the preceding month; i.e. hospital admission for prolonged rest associated with new ischaemic ECG changes and/or a troponin rise.
II. Secondary causes of coronary slow flow including - the no-reflow phenomenon and myocarditis.
III. Secondary causes of angina including - clinically significant anaemia (haemoglobin less than 100g/dL), uncontrolled atrial fibrillation (i.e. ventricular response rate greater than 108 bpm), haemodynamically significant aortic stenosis (estimated mean aortic valve gradient equal to 50mmHg).

Exclusions from contraindications of Consumer Medical Information BRILINTA (Registered Trademark) ticagrelor product information Doc ID-001619899 v4.0
IV. Patients taking regular Aspirin, non-steroidal anti-inflammatory drugs and oral coagulants.
V. Patients scheduled for any surgeries

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)
The Pharmacy Unit at the Queen Elizabeth Hospital will manage the randomisation so all Investigators and Participants are blinded throughout the study and analysis period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Assessment of Ticafrelor’s Anti-angina efficacy will be undertaken via blinded analysis of the angina diary endpoints and will be performed by comparison between patients with respect to treatment order utilizing Mann-Whitney U tests.

Based upon previous experience, the mean total angina episodes expected in this study population is 28+/-31 episodes/month. This study showed 56% of reduction in total angina frequency. Thus using a crossover study design to detect a 50% change in frequency with ticagrelor, 29 patients would be required for 80% power at alpha =0.05. Accounting for dropouts, 35 will be patients recruited.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/04/2016
Actual
25/07/2016
Date of last participant enrolment
Anticipated
1/12/2021
Actual
14/09/2021
Date of last data collection
Anticipated
7/12/2021
Actual
7/12/2021
Sample size
Target
35
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5248 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 12716 0
5011 - Woodville South

Funding & Sponsors
Funding source category [1] 292914 0
Commercial sector/Industry
Name [1] 292914 0
AstraZeneca Pty Ltd
Country [1] 292914 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
University of Adelaide- The Queen Elizabeth Hospital campus
Level 5B- Dept of Medicine,
28, Woodville Road
Woodville South
SA 5011
Country
Australia
Secondary sponsor category [1] 291669 0
None
Name [1] 291669 0
Address [1] 291669 0
Country [1] 291669 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294390 0
Human Research Ethics Committee (The Queen Elizabeth Hospital/Lyell McEwin Hospital/Modbury Hospital)
Ethics committee address [1] 294390 0
Ethics committee country [1] 294390 0
Australia
Date submitted for ethics approval [1] 294390 0
15/01/2015
Approval date [1] 294390 0
28/01/2016
Ethics approval number [1] 294390 0
HREC/15/TQEH/4

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 799 799 0 0
/AnzctrAttachments/370084-Beltrame - HREC Approval - HREC15TQEH4 - TIC.pdf

Contacts
Principal investigator
Name 63394 0
Prof John Beltrame
Address 63394 0
The Queen Elizabeth Hospital
Level 5B Discipline of Medicine
28 Woodville Road
Woodville South, SA, 5011
Country 63394 0
Australia
Phone 63394 0
+61 8 8222 6740
Fax 63394 0
Email 63394 0
[email protected]
Contact person for public queries
Name 63395 0
Sivabaskari Pasupathy
Address 63395 0
The Queen Elizabeth Hospital
Level 2 Basil Hetzel Institute
28 Woodville Road
Woodville South SA 5011
Country 63395 0
Australia
Phone 63395 0
+61 8 8222 7719
Fax 63395 0
Email 63395 0
[email protected]
Contact person for scientific queries
Name 63396 0
Sivabaskari Pasupathy
Address 63396 0
The Queen Elizabeth Hospital
Level 2 Basil Hetzel Institute
28 Woodville Road
Woodville South SA 5011
Country 63396 0
Australia
Phone 63396 0
+61 8 8222 7719
Fax 63396 0
Email 63396 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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15482Ethical approval    370084-(Uploaded-21-03-2022-12-42-19)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseReappraising Ischemic Heart Disease in Women.2023https://dx.doi.org/10.31083/j.rcm2404118
N.B. These documents automatically identified may not have been verified by the study sponsor.