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Trial registered on ANZCTR


Registration number
ACTRN12612000340831
Ethics application status
Not yet submitted
Date submitted
22/03/2012
Date registered
23/03/2012
Date last updated
23/03/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Can pre-operative Ivabradine and/or Atorvastatin prevent heart injury following surgery for neck of femur fracture in elderly patients?
Scientific title
A randomised controlled trial of Ivabradine and Atorvastatin in emergent orthopaedic lower limb surgery for neck of femur fracture in elderly patients: a mechanistic study of peri-operative myocardial injury and its prevention using computed tomography coronary plaque imaging and novel biomarkers of cardiovascular stress and lipid metabolism
Secondary ID [1] 280187 0
Nil
Universal Trial Number (UTN)
U1111-1129-3244
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 286116 0
Fractures 286117 0
Peri-operative myocardial injury 286118 0
Condition category
Condition code
Surgery 286312 286312 0 0
Other surgery
Cardiovascular 286340 286340 0 0
Coronary heart disease
Injuries and Accidents 286341 286341 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised using a computerised block randomisation method with blocks of variable sizes to ensure ‘true’ randomisation and equal numbers in each treatment group. Patients will be randomized to one of four groups in a 1:1:1:1 ratio.
1) No treatment (control group)
2) Atorvastatin orally 80 mg daily till discharge from acute hospital care (to home / rehab)
3) Ivabradine 5mg orally twice daily till discharge from acute hospital care (to home / rehab)
4) Ivabradine 5 mg orally twice daily and atorvastatin orally 80 mg daily till discharge from acute hospital care (to home / rehab)

Treatment would start on randomization prior to surgery which would be as soon as practicable after admission.
Intervention code [1] 284511 0
Prevention
Intervention code [2] 284512 0
Treatment: Drugs
Comparator / control treatment
No treatment
Control group
Active

Outcomes
Primary outcome [1] 286783 0
The frequency (binary outcome) and magnitude (continuous variable) of new myocardial injury following emergent orthopaedic surgery for lower limb fracture as assessed by troponin I, on a per protocol basis.
Timepoint [1] 286783 0
Day 0
Day 1
Day 2
Day 3
Secondary outcome [1] 296644 0
Myocardial infarction according to the universal definition
Timepoint [1] 296644 0
Day 3
Secondary outcome [2] 296645 0
Mean HR over 48 hours Holter monitoring postoperatively
Timepoint [2] 296645 0
48 hours
Secondary outcome [3] 296646 0
Incidence and duration of AF over 48 Holter monitoring postoperatively
Timepoint [3] 296646 0
48 hours
Secondary outcome [4] 296647 0
Serum assays of NT-proBNP, MR-proANP, MR-proADM and CT-proET-1. Samples would be stored at negative 80 degrees prior to testing at external laboratory.
Timepoint [4] 296647 0
Days 0,1,2,3
Secondary outcome [5] 296648 0
Serum assays of sPLA2 and Lp-PLA2 mass and activity
Timepoint [5] 296648 0
Days 0,1
Secondary outcome [6] 296649 0
Platelet activation as measured by VerifyNow P2Y12 assay.
Timepoint [6] 296649 0
Preoperative (day 0)
Secondary outcome [7] 296650 0
Death
Timepoint [7] 296650 0
In hospital
30 days
12 months
Secondary outcome [8] 296651 0
Stroke
Timepoint [8] 296651 0
In hospital
30 days
12 months
Secondary outcome [9] 296652 0
Symptomatic bradycardia or heart block requiring cessation of ivabradine
Timepoint [9] 296652 0
In hospital
Secondary outcome [10] 296653 0
Liver enzyme elevation > 3 times the upper limits of normal
Timepoint [10] 296653 0
In Hospital

Eligibility
Key inclusion criteria
1) Age greater than 60 years
2) Neck of femur fracture with planned surgical treatment within 48 hours
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Current ivabradine use
2) Patients who do not undergo surgical treatment for lower limb fracture for any reason. If such patients were initially enrolled they will be excluded from the analysis, i.e per protocol analysis.
3) Heart rate < 65bpm prior to randomisation
4) Known liver disease or liver enzymes > 3 times the higher limits of normal
5) Pre-operative troponin elevation
6) Artificial pacemakers, sick sinus syndrome or complete heart block
7) Concomittant CYP3A4 inhibitors – ketoconazole, macrolides, cyclosporin, gestodene, antiretrovirals

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be randomised using a computerised block randomisation method with blocks of variable sizes to ensure ‘true’ randomisation and equal numbers in each treatment group using sealed opaque envelopes. Patients will be randomized to one of four groups in a 1:1:1:1 ratio
1) No treatment (control group)
2) Atorvastatin 80 mg daily
3) Ivabradine twice daily (as per protocol)
4) Ivabradine twice daily (as per protocol) and atorvastatin 80 mg daily
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computerised block randomisation method with blocks of variable sizes to ensure ‘true’ randomisation and equal numbers in each treatment group using sealed opaque envelopes.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/04/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284936 0
Hospital
Name [1] 284936 0
Northern hospital
Country [1] 284936 0
Australia
Primary sponsor type
Hospital
Name
Northern hospital
Address
Cardiology Department
The Northern hospital
185 Cooper Street
Epping vic 3076
Country
Australia
Secondary sponsor category [1] 283822 0
None
Name [1] 283822 0
Address [1] 283822 0
Country [1] 283822 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 286945 0
The Northern Health Ethics Committee
Ethics committee address [1] 286945 0
Ethics committee country [1] 286945 0
Australia
Date submitted for ethics approval [1] 286945 0
27/03/2011
Approval date [1] 286945 0
Ethics approval number [1] 286945 0

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

Contacts
Principal investigator
Name 33954 0
Address 33954 0
Country 33954 0
Phone 33954 0
Fax 33954 0
Email 33954 0
Contact person for public queries
Name 17201 0
A/Prof William Van Gaal
Address 17201 0
Director of Cardiology
Northern hospital
185 Cooper Street
Epping Vic 3076
Country 17201 0
Australia
Phone 17201 0
+61384058154
Fax 17201 0
+61384058405
Email 17201 0
william.vangaal@nh.org.au
Contact person for scientific queries
Name 8129 0
A/Prof William Van Gaal
Address 8129 0
Director of Cardiology
Northern hospital
185 Cooper Street
Epping Vic 3076
Country 8129 0
Australia
Phone 8129 0
+61384058154
Fax 8129 0
+61384058405
Email 8129 0
william.vangaal@nh.org.au

No information has been provided regarding IPD availability


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.