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Trial registered on ANZCTR


Registration number
ACTRN12609000174280
Ethics application status
Approved
Date submitted
20/01/2009
Date registered
16/04/2009
Date last updated
27/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study
Scientific title
A randomised controlled trial of the beta-blocker carvedilol versus placebo to reduce cardiovascular morbidity and mortality in high-risk patients receiving dialysis: the Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study
Secondary ID [1] 259820 0
Nil known
Universal Trial Number (UTN)
Trial acronym
BLOCADE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cardiovascular disease 4216 0
end-stage kidney disease
haemodialysis
peritoneal dialysis
4217 0
Condition category
Condition code
Renal and Urogenital 4432 4432 0 0
Kidney disease
Cardiovascular 4433 4433 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is the beta-blocking agent carvedilol taken orally, twice daily. Participants who tolerate 6.25mg twice daily in the active Run-in phase and are randomised to carvedilol will undergo titration of carvedilol from 6.25mg twice daily to 25mg twice daily or the highest tolerated dose.
Intervention code [1] 3932 0
Prevention
Intervention code [2] 3933 0
Treatment: Drugs
Comparator / control treatment
The control will be an identical placebo. Participants who tolerate carvedilol 6.25mg twice daily in the active Run-in phase and are randomised to placebo will undergo titration of placebo from 6.25mg twice daily to 25mg twice daily or the highest tolerated dose in an identical fashion to participants receiving active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 5314 0
Tolerability: 1. The proportion of patients that fail to tolerate carvedilol during the active run-in phase.
Timepoint [1] 5314 0
The active Run-in phase will last six weeks and occur before randomisation.
Primary outcome [2] 5315 0
Tolerability: 2. The proportion of patients that fail to tolerate carvedilol after randomization.
Timepoint [2] 5315 0
Participants will be maintained on study drug for 12 months.
Primary outcome [3] 262373 0
Tolerability: 3. The incidence of major adverse effects. The major adverse effects expected are symptomatic hypotension and symptomatic bradycardia. Symptomatic events will be identified by treating staff, notified to study personnel and reported through the adverse event Case Report Form.
Timepoint [3] 262373 0
This outcome will be assessed in both the Run-in phase (6 weeks before randomisation) and for 12 months after randomisation.
Secondary outcome [1] 8938 0
Change in B-type Natriuretic Peptide (BNP) level between baseline and after 12 months of therapy with study drug. BNP assays will be performed by a central laboratory on stored serum at the end of the study. Both BNP and T-terminal BNP will be measured.
Timepoint [1] 8938 0
BNP will be measured at R0, 6 months and 12 months visit.
Secondary outcome [2] 273651 0
Quality of life will be measured using the EQ5D instrument.
Timepoint [2] 273651 0
Quality of Life (EQ5D) will be measured at Baseline, 6 months and 12 months visit.

Eligibility
Key inclusion criteria
1. The person has end-stage kidney disease and is receiving either haemodialysis or peritoneal dialysis 2. At the time of signing the consent form, the person is: i) Age >50 years, OR ii) Age >18 years with diabetes, OR iii) Age >18 years and has clinical features of cardiovascular disease (myocardial infarction or ischaemic heart disease, ischaemic stroke or peripheral arterial disease).
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Scheduled for live donor transplant within six months. 2. Experienced a cardiovascular event in the previous 3 months. Cardiovascular events include: myocardial infarction, admission for unstable angina, coronary revascularisation procedure, peripheral arterial revascularisation procedure or stroke. 3. Definite contra-indication to beta-blockers, such as: i) second or third degree atrioventricular block unless treated with a permanent pacemaker ii) sick sinus syndrome unless treated with a permanent pacemaker iii) clinically significant reversible bronchospasm iv) previous intolerance to beta-blockers v) other contra-indication 4. Currently taking a beta-blocker, verapamil, diltiazem or moxonidine and the treating nephrologist does not wish to stop these medications in order to enter the trial. 5. Considered by the treating nephrologist to be clinically or haemodynamically unstable for the study. 6. Unstable target weight (defined by a change of >2.0kg in target base weight over the preceding month). 7. Severe hepatic dysfunction (transaminases >3x higher than the upper normal limit) on the most recent liver function tests (if performed within 3 months). 8. Already involved in a clinical trial where the intervention being trialled is likely to confound the outcome of this trial. 9. Considered by the treating physician to have a life expectancy of less than 12 months. 10. Inability to provide consent or follow study instructions due to psychological illness or condition. 12. Pregnant or planning to be pregnant during the trial period.

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)
People who satisfy inclusion and exclusion criteria and who tolerate carvedilol 6.25mg twice daily at the end of the Run-in phase will be randomised to carvedilol or placebo.
Randomisation will be conducted utilising an Interactive Voice Response System (IVRS) to allocate the patient to a trial arm using dynamically allocated methods (Flexetrials, National Health and Medical Research Council Clinical Trials Centre, University of Sydney). Stratification will occur for study site and dialysis modality. Patients will be randomised to one of two treatment groups in equal proportion. Participants will be allocated to medication packs at the site and participants, investigators, and outcome assessors will not know whether the medication pack contains active drug or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised using a computer-generated sequence, with stratification by site and dialysis modality (haemodialysis or peritoneal dialysis).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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,QLD,SA,VIC
Recruitment hospital [1] 1651 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 1652 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 1653 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 1654 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [5] 1655 0
Logan Hospital - Meadowbrook
Recruitment hospital [6] 1656 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 1657 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 1390 0
2050
Recruitment postcode(s) [2] 7538 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [3] 1393 0
2145
Recruitment postcode(s) [4] 1389 0
3052
Recruitment postcode(s) [5] 1391 0
3084
Recruitment postcode(s) [6] 1388 0
3168
Recruitment postcode(s) [7] 1387 0
4102
Recruitment postcode(s) [8] 7539 0
4131 - Meadowbrook
Recruitment postcode(s) [9] 1392 0
5000
Recruitment outside Australia
Country [1] 1539 0
New Zealand
State/province [1] 1539 0
Auckland
Country [2] 1540 0
New Zealand
State/province [2] 1540 0
Middlemore
Country [3] 1541 0
New Zealand
State/province [3] 1541 0
Dunedin

Funding & Sponsors
Funding source category [1] 4395 0
Other Collaborative groups
Name [1] 4395 0
Jacquot Collaborative Research Initiative Grant
Address [1] 4395 0
Royal Australasian College of Physicians
145 Macquarie Street,
Sydney, NSW, 2000
Country [1] 4395 0
Australia
Funding source category [2] 4396 0
Commercial sector/Industry
Name [2] 4396 0
Pfizer Cardiovascular lipid (CVL) Grant
Address [2] 4396 0
CVL Research Grants (Pfizer Australia)
38-42 Wharf Road
West Ryde NSW 2114
Country [2] 4396 0
Australia
Funding source category [3] 264698 0
Government body
Name [3] 264698 0
New Zealand Health Research Council Feasibility Study Grant 10/163
Address [3] 264698 0
Level 3 - ProCare Building
110 Stanley Street - access via Grafton Mews
Auckland 1010
Country [3] 264698 0
New Zealand
Funding source category [4] 264699 0
Government body
Name [4] 264699 0
National Health and Medical Research Council Project Grant APP1006171
Address [4] 264699 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [4] 264699 0
Australia
Primary sponsor type
University
Name
Australasian Kidney Trials Network- University of Queensland
Address
The University of Queensland
School of Medicine
Building 33, Ground Level
Princess Alexandra Hospital
Ipswich Road
Woolloongabba Qld 4102
Country
Australia
Secondary sponsor category [1] 3955 0
None
Name [1] 3955 0
Address [1] 3955 0
Country [1] 3955 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6445 0
Medical Research Ethics Committee, University of Queensland
Ethics committee address [1] 6445 0
The University of Queensland
Brisbane St Lucia QLD 4072
Ethics committee country [1] 6445 0
Australia
Date submitted for ethics approval [1] 6445 0
Approval date [1] 6445 0
03/09/2010
Ethics approval number [1] 6445 0
2009000775

Summary
Brief summary
The BLOCADE Feasibility Study aims to inform the final design of a randomised controlled trial with clinically important endpoints to determine whether therapy with the beta-blocker carvedilol will reduce the cardiovascular morbidity and mortality of patients receiving dialysis. The major aim of the Feasibility Study is thus to determine the tolerability of carvedilol in this population.
Participants will be patients over the age of 50 years, or those over 18 years with either diabetes or cardiovascular disease. After a run-in phase, patients will be randomised to carvedilol, titrated to the maximum tolerated dose or 25mg twice daily, or placebo titrated in an identical fashion. Patients will be followed for 12 months to determine tolerability in terms of the proportion of participants not tolerating carvedilol in the Run-in Phase and post Randomisation, as well as the incidence of major adverse effects. Other data such as rates of dropping out or dropping in will specifically inform the final sample size calculation, and data regarding recruitment rates and the numbers of patients tolerating each specific dose of carvedilol will assist with logistics. The Feasibility Study will recruit 150 participants and follow them for 12 months, at which time they will have a final study visit, then undergo supervised down-titration then cessation of study drug.
The protocol of the proposed Clinical End-point Study will be written based on data from the Feasibility Study.
Trial website
http://www.aktn.org.au/trials/recruiting.php
Trial related presentations / publications
The ß-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) Feasibility Study: A Randomized Controlled Trial.
Roberts MA, Pilmore HL, Ierino FL, Badve SV, Cass A, Garg AX, Isbel NM, Krum H, Pascoe EM, Perkovic V, Scaria A, Tonkin AM, Vergara LA, Hawley CM; BLOCADE Study Collaborative Group.
Am J Kidney Dis. 2015 Dec 22. pii: S0272-6386(15)01394-3. doi: 10.1053/j.ajkd.2015.10.029.
PMID: 26717861
Public notes

Contacts
Principal investigator
Name 35103 0
Dr Matthew Roberts
Address 35103 0
Eastern Health Integrated Renal Service
Level 2 | 5 Arnold Street | Box Hill VIC 3128
Country 35103 0
Australia
Phone 35103 0
+61 3 90952410
Fax 35103 0
+61 3 98996810
Email 35103 0
Matthew.Roberts@easternhealth.org.au
Contact person for public queries
Name 12450 0
Dr Liza Vergara
Address 12450 0
Australasian Kidney Trials Network
The University of Queensland School of Medicine
Building 33, Ground Level
Princess Alexandra Hospital
Ipswich Road
Woolloongabba Qld 4102
Country 12450 0
Australia
Phone 12450 0
+61 7 3176 5394
Fax 12450 0
+61 7 3176 5663
Email 12450 0
l.vergara@uq.edu.au
Contact person for scientific queries
Name 3378 0
Dr Dr Matthew Roberts
Address 3378 0
Eastern Health Integrated Renal Service
Level 2 | 5 Arnold Street | Box Hill VIC 3128
Country 3378 0
Australia
Phone 3378 0
+61 3 90952410
Fax 3378 0
+61 3 98996810
Email 3378 0
Matthew.Roberts@easternhealth.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary