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Trial registered on ANZCTR


Registration number
ACTRN12618000672257
Ethics application status
Approved
Date submitted
15/08/2017
Date registered
24/04/2018
Date last updated
2/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Cardiac Magnetic Resonance Imaging in Heart Transplant Rejection Detection
Scientific title
Randomised Safety Outcomes Study Comparing Patients Diagnosed and Treated for Acute Cardiac Rejection on Cardiac MR Compared to Endomyocardial Biopsy
Secondary ID [1] 292660 0
None
Universal Trial Number (UTN)
U1111-1200-7442
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Transplant Recipients 304399 0
Cardiac Allograft Rejection 304400 0
Condition category
Condition code
Cardiovascular 303728 303728 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention Group- Cardiac MR based protocols will be used for screening for cardiac transplant allograft rejection as opposed to traditional endomyocardial biopsy
Consultant Cardiologist and Research Fellow Will be Supervising and Reporting the Cardiac MRI scans
Cardiac MRI protocol involved undergoing a cardiac MRI scan. This takes 30 minutes including the wait time.
Visits will be as per the biopsy clinic protocol

The screening protocols are part of the pre -existing protocol at St Vincent's Hospital and the fidelity to the intervention will have to be monitored by the reporting consultant cardiologist and the trial coordinator as the intervention group will only have CMR based protocols for screening for rejection.


The same Cardiac MRI consultant will be reporting all the scans therefore there will be no inter-reporter variability
Fortnightly for 3 months
3 monthly for the subsequent 3 months
Monthly for the subsequent 3 months
And 2 final scans at month 11 and 12 post transplant


Intervention code [1] 298894 0
Early detection / Screening
Intervention code [2] 300632 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator is endomyocardial biopsy which is an invasive procedure where histology is obtained by obtaining specimens from the patients right interventricular septum using a bioptome.

Samples obtained are then sent for histopathological analysis by two histopathologist at St Vincents Hospital independently.

The biopsies are performed at the same intervals as the CMR.
This is fortnightly from week 6 post transplant for 3 months;
Monthly For 3 months
1 at month 9
1 at month 12
Control group
Active

Outcomes
Primary outcome [1] 303099 0
Each outcome will be analysed throughout the follow up period of 12 months individually by marking down an outcome event and analysing them at the end of the study period .

A spreadsheet will be created and whenever a participant has an episode of rejection this will be entered and tabulated at the end of the study period.

Frequeuncy of rejection will be determined by Cardiac MRI in the CMR group and Biopsy results in the biopsy group
Timepoint [1] 303099 0
12 months post enrolment will be the end point cutoff
Primary outcome [2] 305260 0
Frequency and severity of serious infections

Each infection episode will be added to the spreadsheet at time of diagnosis by treating physician and tabulated at the end of the study period
Timepoint [2] 305260 0
12 months of follow up
Primary outcome [3] 305261 0
Biopsy - related complications : carotid dissection, neck haematoma, tricuspid incompetence, right ventricular puncture and cardiac effusion, cardiac tamponade, dysrhythmia

Any complications due to the procedure of endomyocardial biopsy will be entered into a spreadsheet and tabulated at the end of the study
Timepoint [3] 305261 0
In 12 months of follow up
Secondary outcome [1] 337883 0
Frequency and severity of cardiac allograft vasculopathy as determined by CTCA or Invasive angiography at 1 year

This is a composite outcome

Timepoint [1] 337883 0
12 months post enrolment into study
Secondary outcome [2] 344653 0
Total immunosuppression required

The doses of immunosuppressant's at twice weekly clinic visits will be entered into a spreadsheet and compared across the two groups.
Timepoint [2] 344653 0
in 12 months of follow up
Secondary outcome [3] 344654 0
Measures of tissue characterisation and myocardial performance by CMR and CMR based strain.

T1 and T2 relaxation times are measures of tissue characterisation and circumfrential strain is used for strain analysis

Timepoint [3] 344654 0
Monthly for 12 months
Secondary outcome [4] 344655 0
Death.

This will be from hospital records.

Timepoint [4] 344655 0
In 12 months of follow up
Secondary outcome [5] 344877 0
All cause hospitalisation- review of medical records
Timepoint [5] 344877 0
12 months post enrolment into study
Secondary outcome [6] 344878 0
Cardiovascular hospitalisation - medical records
Timepoint [6] 344878 0
12 months post enrolment into study

Eligibility
Key inclusion criteria
Stable Recipient of orthotopic heart transplant 4 weeks post transplant
No contraindication to cardiac MRI
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindication to cardiac MRI

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Nil
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomiser
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis
Normality testing will be employed using the Shapiro-Wilks test. Parametric data will be analysed using student’s t-test, Fisher’s exact test and McNemar’s test. Non-parametric data will be analysed using the Mann-Whitney U test and Wilcoxon ranked sum test.
Correlations will be explored using Pearson’s correlation coefficient, Spearman’s Rho and contingency coefficients as appropriate.
Regression analysis will be undertaken to investigate the predictive effect of treatment findings on primary safety outcomes. This will involve Binary logistic analysis and multiple linear regression analysis as appropriate.
Kaplan-Meier curves will be utilised to illustrate the time-to-event for our primary outcomes, and the difference in treatment groups

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] 8806 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 16929 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 297293 0
Charities/Societies/Foundations
Name [1] 297293 0
National Heart Foundation
Address [1] 297293 0
Level 3, 80 William Street

East Sydney NSW 2011
Country [1] 297293 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Victor Chang Cardiac Research Institute
Address
405 Liverpool Street, Darlinghurst New South Wales 2010
Country
Australia
Secondary sponsor category [1] 296264 0
None
Name [1] 296264 0
Address [1] 296264 0
Country [1] 296264 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298403 0
St Vincents Hospital Research Office
Ethics committee address [1] 298403 0
97-105 Boundary Street Darlinghurst 2010 New South Wales , Sydney
Ethics committee country [1] 298403 0
Australia
Date submitted for ethics approval [1] 298403 0
09/03/2017
Approval date [1] 298403 0
06/06/2017
Ethics approval number [1] 298403 0
NEAF AU/15B1c212

Summary
Brief summary
Comparing safety outcomes of patients treated based on Cardiac MR/ imaging screening of acute rejection compared to endomyocardial biopsy guided screening. The imaging technniques used will be a combination of tissue characterisation, strain and ventricular function on CMR and TTE.
Objectives:
Primary Safety Outcomes Endpoints 1) Frequency and severity of cardiac rejection
2) Frequency and severity of serious infections
3) Cardiovascular morbidity
4) Cardiovascular hospitilisation
5) All cause for hospitilization
6) Death
7) Biopsy - related complications
8) Frequency and severity of cardiac allograft vasculopathy as determined by CTCA or Invasive angiography at 1 year
9) Total immunosuppression required
10) Measures of tissue characterisation and myocardial performance by CMR and TTE utilising in addition CMR strain and TTE global longitudinal strain

Trial website
None
Trial related presentations / publications
Public notes
None

Contacts
Principal investigator
Name 76974 0
Dr Chris Anthony
Address 76974 0
St Vincents Hospital Sydney 290 Victoria Street Darlinghurst 2010 New South Wales
Country 76974 0
Australia
Phone 76974 0
+61283821111
Fax 76974 0
Email 76974 0
canthony@stvincents.com.au
Contact person for public queries
Name 76975 0
Dr Chris Anthony
Address 76975 0
St Vincents Hospital Sydney 290 Victoria Street Darlinghurst 2010 New South Wales
Country 76975 0
Australia
Phone 76975 0
+61283821111
Fax 76975 0
Email 76975 0
canthony@stvincents.com.au
Contact person for scientific queries
Name 76976 0
Dr Chris Anthony
Address 76976 0
St Vincents Hospital Sydney 290 Victoria Street Darlinghurst 2010 New South Wales
Country 76976 0
Australia
Phone 76976 0
+61283821111
Fax 76976 0
Email 76976 0
canthony@stvincents.com.au

No information has been provided regarding IPD availability
Summary results
No Results