Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000387628
Ethics application status
Approved
Date submitted
31/03/2014
Date registered
9/04/2014
Date last updated
9/04/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Everolimus for the prevention of calcineurin-inhibitor-induced left ventricular hypertrophy in heart transplantation
Scientific title
An open label randomised study comparing the role of combination of everolimus and low dose tacrolimus with full dose tacrolimus in the prevention of left ventricular hypertrophy in heart transplant recepients.
Secondary ID [1] 284333 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
RAD-TAC study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Left ventricular hypertrophy in heart transplantation 291490 0
Condition category
Condition code
Cardiovascular 291856 291856 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RADTAC arm: Everolimus tablets, administered orally, twice daily in combination with low dose tacrolimus, mycophenolate +/- predinsolone, all taken orally, commenced at 3 months post transplantation and continued for at least 9 months. The Everolimus will be started at 0.5mg twice daily and then adjusted according to the plasma level aiming 3-8 mcg/lit. The tacrolimus dose will be started at 0.5mg twice daily and then adjusted according to the plasma levels aiming 2-5mcg/lit. The Mycophenolate dose will 1000-2000mg twice daily and prednisole maintenance dose will be 7.5-10mg daily as per current standard of care for heart transplantation.
To improve the patient`s adherence to the treatment, they will be asked about the medications and doses they have been taking as well as encouraged to take medications at each clinical visit.
Their adherence will be monitored by checking plasma drug levels at each clinical visit.
Intervention code [1] 289057 0
Treatment: Drugs
Intervention code [2] 289138 0
Prevention
Comparator / control treatment
TAC arm: The current standard treatment in the form of tacrolimus tablets, administered orally, twice daily in combiantion with oral mycophenolate +/- oral predinsolone. The tacrolimus dose will be started at 0.5mg twice daily and then adjusted according to the plasma levels aiming 6-10mcg/lit. The Mycophenolate dose will 1000-2000mg twice daily and prednisole maintenance dose will be 7.5-10mg daily as per current standard of care for heart transplantation.
Control group
Active

Outcomes
Primary outcome [1] 291768 0
Left ventricular mass index as measured by cardiac magnetic resonance imaging (CMR) at one year post heart transplantation.
Timepoint [1] 291768 0
9 months and 33 months (12 months and 36 months post heart transplantation).
Secondary outcome [1] 307476 0
Systemic blood Pressure measured manually with sphygmomanometer.
Timepoint [1] 307476 0
9 months and 33 months (12 months and 36 months post heart transplantation).
Secondary outcome [2] 307477 0
Novel measures of fibrosis by CMR and blood markers.
Timepoint [2] 307477 0
9 months and 33 months (12 months and 36 months post heart transplantation).
Secondary outcome [3] 307478 0
Estimated glomerulatr filtration rate (eGFR).
Timepoint [3] 307478 0
9 months and 33 months (12 months and 36 months post heart transplantation).

Eligibility
Key inclusion criteria
Stable orthotopic heart transplant recipients at 3-months after heart transplantation and willingness to provide informed consent.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Hemodynamic instability at 10 weeks after transplantation, greater than 2 x 3A rejection or single 3B rejection, ongoing sepsis at 10 weeks after transplantation, ongoing wound dehiscence or infection at 10 weeks after transplantation, end-stage renal failure requiring dialysis at 10 weeks after transplantation, and contraindication to cardiovascular magnetic resonance scanning

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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software i.e. computerised sequence generation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 0
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We calculated the sample size from LV Mass index Outcome based on CMR data from Grothues et al. Based on a standard deviation of 4.4 g/m2 a study of 30 patients with 2 arms (90%power and alpha error of 0.05) would allow a 5.26g/m2 difference to be detected. To allow for approximately 30% dropout we aim to recruit 40 patients to the study
Statistical methods to be employed include t-tests, analysis of variance, analysis of covariance repeated measures ANOVA as appropriate for parametric data and Mann-Whitney, Wilcoxon Signed Rank, and Friedman tests as appropriate for non-parametric data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/04/2014
Actual
Date of last participant enrolment
Anticipated
2/04/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 2272 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 2282 0
The Alfred - Prahran
Recruitment hospital [3] 2283 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 2284 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 7960 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 7961 0
3181 - Prahran
Recruitment postcode(s) [3] 7962 0
4032 - Chermside
Recruitment postcode(s) [4] 7963 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 289005 0
Hospital
Name [1] 289005 0
St. Vincents hospital, NSW
Country [1] 289005 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent`s Hospital
Address
390 Victoria street, Darlinghurst, NSW 2010
Country
Australia
Secondary sponsor category [1] 287683 0
None
Name [1] 287683 0
Address [1] 287683 0
Country [1] 287683 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290814 0
St. Vincent`s Hospital HREC
Ethics committee address [1] 290814 0
St. Vincent`s research office, Level 6 Delacy building,
390 Victoria street, Darlinghurst, NSW 2010
Ethics committee country [1] 290814 0
Australia
Date submitted for ethics approval [1] 290814 0
14/11/2013
Approval date [1] 290814 0
10/12/2013
Ethics approval number [1] 290814 0
HREC/13/SVH/345

Summary
Brief summary
The primary purpose of the study is to assess left ventricular hypertrophy prevention at 1 year after heart transplantation with everolimus in combination with low-dose calcineurin inhibitors compared to full-dose calcineurin inhibitors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47246 0
Prof Peter Macdonald
Address 47246 0
St. Vincent`s hospital, 390 Victoria street, Darlinghurst, NSW 2010
Country 47246 0
Australia
Phone 47246 0
+61-2-83821111
Fax 47246 0
Email 47246 0
[email protected]
Contact person for public queries
Name 47247 0
A/Prof Andrew Jabbour
Address 47247 0
St. Vincent`s hospital, 390 Victoria street, Darlinghurst, NSW 2010
Country 47247 0
Australia
Phone 47247 0
+61-2-83821111
Fax 47247 0
Email 47247 0
[email protected]
Contact person for scientific queries
Name 47248 0
A/Prof Andrew Jabbour
Address 47248 0
St. Vincent`s hospital, 390 Victoria street, Darlinghurst, NSW 2010
Country 47248 0
Australia
Phone 47248 0
+61-2-83821111
Fax 47248 0
Email 47248 0
[email protected]

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.