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Trial registered on ANZCTR


Registration number
ACTRN12611000203954
Ethics application status
Approved
Date submitted
10/02/2011
Date registered
21/02/2011
Date last updated
11/03/2019
Date data sharing statement initially provided
11/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Ivabradine study - Assessing the benefit of Ivabradine in reducing episodes of angina in patients with chronic refractory angina.
Scientific title
A Placebo-controlled, Randomised, Double-blind, Crossover Study of the Efficacy of Ivabradine in the Management of Chronic Refractory Angina.
Secondary ID [1] 253311 0
nil
Universal Trial Number (UTN)
U1111-1118-7136
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic refractory angina 258846 0
Condition category
Condition code
Cardiovascular 258984 258984 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two arms in this study. Randomise to Placebo/Ivabradine 5mg-7.5mg bd (double-blind methodology).

Treatment A: placebo/Ivabradine 5mg orally twice daily. Continue therapy over a 2-week period prior to a titration visit to assess efficacy and tolerability.
At 2-week follow-up period, if angina symptoms persist, up-titrate to placebo/ivabradine 7.5mg bd, and continue therapy for 4 weeks until assessment of endpoints.

A drug washout period of 2 weeks will then ensue followed by cross-over to alternate study phase and repeat of the above protocol over a 6-week period.

Treatment B: One placebo/ivabradine capsule orally twice daily, same as treatment arm A
Intervention code [1] 257764 0
Treatment: Drugs
Intervention code [2] 257765 0
Prevention
Comparator / control treatment
Primary component of the placebo capsules is microcrystalline cellulose.

Treatment B: One placebo capsule orally twice daily for 6 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 259839 0
In patients with chronic refractory angina, ivabradine 5mg to 7.5mg twice-daily will reduce the Angina Frequency score, as measured on the Seattle Angina Questionnaire (SAQ) by a mean of 10 points compared to placebo.
Timepoint [1] 259839 0
SAQ's will be administered at baseline, week 6 and week 14.
Secondary outcome [1] 268693 0
Reduce sublingual nitrate consumption as compared with placebo. This will be assessed by reviewing the angina diary that the patient completes
Timepoint [1] 268693 0
sublingual nitrate consumption use will be assessed at each study visit over the 14 week trial (week 0, week 2, week 6, week 8, week 10 and week 14).
Secondary outcome [2] 268694 0
Improve the Seattle Angina Questionnaire domain components (physical limitation, quality of life, treatment satisfaction, angina stability and frequency).
Timepoint [2] 268694 0
SAQ's will be administered at baseline, week 6 and week 14.
Secondary outcome [3] 268695 0
Reduce the frequency of spontaneous anginal episodes over a 4-week period. This will be assessed by reviewing the angina diary that the patient completes
Timepoint [3] 268695 0
Anginal episodes will be evaluated at each trial visit over the 14 week trial (week 0, week 2, week 6, week 8, week 10 and week 14).
Secondary outcome [4] 268696 0
Improve 6-minute walk distances.
Timepoint [4] 268696 0
6-minute walk distances will be assessed at weeks 6 and 14.

Eligibility
Key inclusion criteria
Chronic Refractory Angina is continuing despite conventional anti anginal therapy, ie:
-Beta Blocker, Calcium channel blocker, Long acting nitroglycerin, nicorandil
-CAD is not amenable to revascularisation therapy
-There has been a stable anginal pattern over the past month


defined as:
(a) Objective evidence of coronary artery disease (1mm ST depression on stress ECG test, reversible defect on stress myocardial scintigraphy, or >70% coronary stenosis on angiography)
(b) Continuing angina despite ‘conventional antianginal therapy’. That is, patients must have been shown to be treated with or not treated with due to intolerance/contraindicated/ inefficacy to a beta blocker (BB) AND treated with or not treated with due to intolerance/contraindicated/inefficacy a calcium channel blocker (CCB) AND treated with or not treated with due to intolerance/ contraindicated/ inefficacy a long acting nitrate (LAN) AND treated with or not treated with due to intolerance/ contraindicated/ inefficacy nicorandil.
(c) Coronary artery disease not amenable to revascularisation therapy either due to unsuitable coronary anatomy or patient characteristics.
(d) Stable anginal pattern for the past month.
3. Symptomatic angina with episodes occurring 3 times/week
4. Sinus rhythm
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient must not have had an Acute coronary syndrome admission within the past 3 months, or a revascularisation procedure within the past 6 months or planned within the next 3 months.
Resting heart rate cannot be under 60bpm on an ECG.
Blood pressure must not be under 90/50 mm/Hg.
Patients are not allowed to use conomitant non-dyhydropyridine calcium channel blocker therapy.
Patient must be able to provide informed consent.

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)
Patients who successfully complete the screening assessments will be randomised into the study.
Patient study number will be allocated in chronological order by Study Co-ordinator. Patient study number and drug pack number will be the same.
Copies of the randomisation code will be kept by the clinical trial pharmacist.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer based program “Research Randomiser” was used to produce a paper based randomisation list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Placebo-controlled, Double-blind
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
17/12/2010
Actual
24/03/2011
Date of last participant enrolment
Anticipated
Actual
3/05/2012
Date of last data collection
Anticipated
Actual
11/11/2013
Sample size
Target
30
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 258230 0
Commercial sector/Industry
Name [1] 258230 0
SERVIER LABORATORIES (AUST) PTY LTD
Country [1] 258230 0
Australia
Primary sponsor type
Hospital
Name
The Queen Elizabeth Hospital
Address
28 Woodville Road,
Woodville South
South Australia 5011
Country
Australia
Secondary sponsor category [1] 257428 0
None
Name [1] 257428 0
Address [1] 257428 0
Country [1] 257428 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260210 0
Central Northern Adelaide Health Service, The Queen Elizabeth Hospital
Ethics committee address [1] 260210 0
Ethics committee country [1] 260210 0
Australia
Date submitted for ethics approval [1] 260210 0
Approval date [1] 260210 0
23/08/2010
Ethics approval number [1] 260210 0
2010068

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32028 0
Prof John Beltrame
Address 32028 0
The Queen Elizabeth Hospital
28 Woodville Road
Woodville
SA 5011
Country 32028 0
Australia
Phone 32028 0
+61 8 8222 6000
Fax 32028 0
Email 32028 0
[email protected]
Contact person for public queries
Name 15275 0
Professor John Beltrame
Address 15275 0
28 Woodville Road
Woodville South
South Australia 5011
Country 15275 0
Australia
Phone 15275 0
+61 8 8222 6000
Fax 15275 0
+61 8 8222 7201
Email 15275 0
[email protected]
Contact person for scientific queries
Name 6203 0
Professor John Beltrame - Principal Investigator
Address 6203 0
28 Woodville Road
Woodville South
South Australia 5011
Country 6203 0
Australia
Phone 6203 0
+61 8 8222 6000
Fax 6203 0
+61 8 8222 7201
Email 6203 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
trial ceased due to lack of suitable candidates


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.