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Trial registered on ANZCTR


Trial ID
ACTRN12613000762752
Ethics application status
Approved
Date submitted
26/06/2013
Date registered
9/07/2013
Date last updated
9/07/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Mortality among dialysis patients prescribed sevelamer hydrochloride and lanthanum carbonate compared with calcium-based phosphate binders: A retrospective cohort study using the Australian and New Zealand Dialysis and Transplant Database (ANZDATA).
Scientific title
All cause and cardiovascular mortality among Australian adult dialysis patients prescribed sevelamer hydrochloride and lanthanum carbonate compared with calcium-based phosphate binders.
Secondary ID [1] 282739 0
Nil
Universal Trial Number (UTN)
U1111-1145-0348
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease stage 5D (dialysis) 289377 0
All cause mortality and cardiovascular mortality 289378 0
calcium and non calcium-based phosphate binders 289379 0
Condition category
Condition code
Renal and Urogenital 289739 289739 0 0
Kidney disease

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
6
Target follow-up type
Years
Description of intervention(s) / exposure
This is a retrospective observational study to assess whether the introduction of non calcium based phosphate binders sevelamer hydrochloride (Renagel) and lanthanum carbonate (Fosrenal) over the past 6-7 years has influenced the mortality of patients on dialysis.
Intervention code [1] 287335 0
Not applicable
Comparator / control treatment
Patients not using the newer non calcium-based binders will be the comparator group.
Control group
Active

Outcomes
Primary outcome [1] 289804 0
All cause mortality as assessed by data linkage of dialysis patient information stored on the Australian and New Zealand Dialysis and Transplant database (ANZDATA) and the pharmaceutical prescription data stored on the Australian Pharmaceutical Benefits Scheme (PBS) database.
Timepoint [1] 289804 0
Time point: Data collected up to July 31st 2013.
Baseline data to assess mortality prior to introduction of these agents in 2007 will begin In 2002, 5 years before their introduction.
Secondary outcome [1] 303331 0
Cardiovascular mortality as assessed by data linkage of dialysis patient information stored on the ANZDATA database and the pharmaceutical prescription data stored on the PBS database.
Timepoint [1] 303331 0
Time point: Data collected up to July 31st 2013.
Baseline data to assess mortality prior to introduction of these agents in 2007 will begin In 2002, 5 years before their introduction.

Eligibility
Key inclusion criteria
Australian dialysis patients aged over 18 years of age and registered in ANZDATA registry will be included in the study.
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
New Zealand patients and patients aged less than 18 years of age in ANZDATA registry will be excluded

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
There are currently over 10,000 Australians on dialysis in the ANZDATA registry, and approximately 2,500 new patients commence dialysis each year. Therefore over the 6-7 years since introduction of non calcium-based binders, we will be able to follow approximately 15,000 patients to death, transplantation or to the end of the study period.

Statistical analyses will include calculation of all-cause and cardiovascular disease mortality rates before and after the introduction of the non calcium-based phosphate binders and mortality rates will be examined within age and sex categories to examine changes in mortality within dialysis patient sub-groups. Changes in the usage of non calcium-based phosphate binders will be examined overall and within dialysis patient sub-groups. A series of survival analyses will then be conducted to examine whether there is a survival advantage conferred by the use of the newer drugs and these will include Cox models, controlling for covariates (such as presence of concomitant illness such as diabetes, age, dialysis vintage, hours and adequacy, use of other drugs that may influence mortality and centre effects), all of which may affect patient survival. The analysis will be conducted using Excel and SPSS software packages.

Recruitment
Recruitment status
Active, not 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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 1164 0
Westmead Hospital - Westmead

Funding & Sponsors
Funding source category [1] 287469 0
Self funded/Unfunded
Name [1] 287469 0
NA
Address [1] 287469 0
NA
Country [1] 287469 0
Primary sponsor type
Individual
Name
A/Prof Grahame Elder
Address
Department of Renal Medicine, Westmead Hospital
Cnr Hawkesbury Road and Darcy Road, Westmead NSW 2145

Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 286213 0
Individual
Name [1] 286213 0
A/Prof Jacqueline Center
Address [1] 286213 0
1. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
2. Department of Endocrinology, St Vincents Hospital, 390 Victoria St Darlinghurst NSW 2010
Country [1] 286213 0
Australia
Secondary sponsor category [2] 286214 0
Individual
Name [2] 286214 0
A/Prof R Louise Rushworth
Address [2] 286214 0
School of Medicine, University of Notre Dame,
160 Oxford Street, Darlinghurst NSW 2010
Country [2] 286214 0
Australia
Secondary sponsor category [3] 286215 0
Individual
Name [3] 286215 0
Dr Lorraine Pereira
Address [3] 286215 0
Blacktown Hospital, 18 Blacktown Rd Blacktown NSW 2148
Country [3] 286215 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289445 0
HREC: Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 289445 0



Western Sydney Local Health District HREC
Research Office
Westmead Hospital
Rm 2020
Clinical Sciences Building
WESTMEAD NSW 2145
Ethics committee country [1] 289445 0
Australia
Date submitted for ethics approval [1] 289445 0
08/05/2013
Approval date [1] 289445 0
Ethics approval number [1] 289445 0
13/2013
Ethics committee name [2] 289446 0
Department of Health and ageing (DoHA)
Ethics committee address [2] 289446 0
Department of Health and Ageing
Portfolio Strategies Division MDP 132
GPO Box 9848
Canberra ACT 2601
Ethics committee country [2] 289446 0
Australia
Date submitted for ethics approval [2] 289446 0
29/05/2013
Approval date [2] 289446 0
02/07/2013
Ethics approval number [2] 289446 0
Ethics committee name [3] 289447 0
Australian and New Zealand Dialysis and Transplant Registry ( ANZDATA)
Ethics committee address [3] 289447 0
ANZDATA Registry
Level 9 East Wing, Room C9-32
The Royal Adelaide Hospital
DX 800 - Mail Point 117
SA
Ethics committee country [3] 289447 0
Australia
Date submitted for ethics approval [3] 289447 0
01/07/2013
Approval date [3] 289447 0
Ethics approval number [3] 289447 0
Ethics committee name [4] 289448 0
Australian Institute of Health and Welfare ( AIHW)
Ethics committee address [4] 289448 0
Ethics committee country [4] 289448 0
Australia
Date submitted for ethics approval [4] 289448 0
01/07/2013
Approval date [4] 289448 0
Ethics approval number [4] 289448 0

Summary
Brief summary
The proposed study is a national, retrospective cohort study, which aims to determine if the introduction of non calcium-based phosphate binders sevelamer hydrochloride and lanthanum carbonate, since their PBS listing in 2007/2008, has been associated with a change in all-cause or cardiovascular disease mortality.

We hypothesize that for patients on dialysis, most of whom require the use of phosphate binding medication, the progressive displacement of traditional calcium-based phosphate binders by the non calcium-based drugs sevelamer hydrochloride (Renagel) and lanthanum carbonate (Fosrenal) will have reduced cardiovascular and/or all-cause mortality after adjustment for covariates.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40774 0
A/Prof Grahame Elder
Address 40774 0
1. Department of Renal Medicine, Westmead Hospital,
Cnr Hawkesbury Road and Darcy Road, Westmead NSW 2145
2. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country 40774 0
Australia
Phone 40774 0
+61 412 357 246
Fax 40774 0
+61 2 96339351
Email 40774 0
g.elder@garvan.org.au
Contact person for public queries
Name 40775 0
Dr Lorraine Pereira
Address 40775 0
Blacktown Hospital,
18 Blacktown Rd Blacktown NSW 2148
Country 40775 0
Australia
Phone 40775 0
+61 422223782
Fax 40775 0
Email 40775 0
l.l.pereira@smd12.qmul.ac.uk
Contact person for scientific queries
Name 40776 0
A/Prof Grahame Elder
Address 40776 0
1. Department of Renal Medicine, Westmead Hospital,
Cnr Hawkesbury Road and Darcy Road, Westmead NSW 2145
2. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, 384 Victoria St Darlinghurst NSW 2010
Country 40776 0
Australia
Phone 40776 0
+61 412 357 246
Fax 40776 0
+61 2 96339351
Email 40776 0
g.elder@garvan.org.au