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Trial registered on ANZCTR


Registration number
ACTRN12610000650099
Ethics application status
Approved
Date submitted
9/08/2010
Date registered
10/08/2010
Date last updated
5/02/2019
Date data sharing statement initially provided
5/02/2019
Date results information initially provided
5/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
IMPROVE: IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease
Scientific title
A randomised, double-blind, placebo-controlled trial to assess the effect of phosphate reduction with lanthanum carbonate on arterial compliance and vascular calcification in patients with chronic kidney disease stages 3b-4.
Secondary ID [1] 252396 0
Nil
Universal Trial Number (UTN)
Trial acronym
IMPROVE-CKD Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phosphate imbalance (as a risk factor for cardiovascular disease) in patients with Chronic Kidney Disease 257906 0
Condition category
Condition code
Renal and Urogenital 258072 258072 0 0
Kidney disease
Cardiovascular 258092 258092 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
lanthanum carbonate (500mg 3x daily)
administration: chewable (oral) tablets
duration of treatment: 24 months
Intervention code [1] 256963 0
Treatment: Drugs
Comparator / control treatment
matched placebo (3x daily)
administration: chewable tablets
duration of treatment: 24 months

Placebo that is undistingishable from the active treatment but containing no active ingredients
Control group
Placebo

Outcomes
Primary outcome [1] 258935 0
Arterial compliance (measured by pulse wave velocity) as a surrogate marker of cardiovascular morbidity and mortality
Timepoint [1] 258935 0
At baseline and at 6 months, 12 months, 18 months and 24 months post randomisation
Secondary outcome [1] 265103 0
Aortic calcification measured with Computed Tomography (CT)
Timepoint [1] 265103 0
At baseline and 24 months post randomisation.
Secondary outcome [2] 265104 0
Serum Phospate, Calcium, calcium phosphate product and parathyroid hormone levels
Timepoint [2] 265104 0
At baseline and at 3, 6, 9, 12, 15, 18, 21, and 24 months post randomisation
Secondary outcome [3] 265105 0
renal function, measured by estimated Glomerular Filtration Rate (eGFR) and % change
Timepoint [3] 265105 0
At baseline and at 12 months and 24 months post randomisation
Secondary outcome [4] 265106 0
Bone mineral density, measured by CT of the lumbar spine
Timepoint [4] 265106 0
At baseline and 24 months post randomisation

Eligibility
Key inclusion criteria
Patients with Chronic Kidney Disease (CKD) Stages 3b-4 (eGFR between 15-44ml/ min/1.73m2) 2. Serum phosphate level greater than 1.00mmol/L on at least 1 occasion over the previous 6 months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study
2. Renal transplantation
3. Recent (within 1 month) hospitalisation or cardiovascular event
4. Pregnancy or breast feeding
5. Medical conditions that impact on phosphate metabolism (apart from CKD), eg. primary hyperparathyroidism or hypoparathyroidism; previous subtotal parathyroidectomy; gastrointestinal malabsorption disorders such as Crohn’s disease, ulcerative colitis, coeliac disease or severe liver dysfunction
6. Malnutrition, defined as serum albumin <30g/L
7. Presence of atrial fibrillation
8. Inability to obtain a pulse wave velocity

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)
Screening will occur when subjects come for their usual visit to their treating physician. The patient will have an initial consultation with a study renal physician to discuss study participation. This will include a preliminary eligibility check.
Randomisation will occur on the day that trial consent is obtained or within 1 week of consent being obtained. This will include a check to ensure that the patient is still eligible. Randomisation will be conducted utilising a web-based database to allocate the patient to a trial arm using dynamically allocated methods.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratification will occur for study site, the patient’s stage of CKD, age and presence of diabetes mellitus. Patients will be randomised to one of two treatment groups in equal proportion.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
A randomised, double-blind, placebo-controlled trial
Phase
Phase 3 / Phase 4
Type of endpoint(s)
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] 2237 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 2238 0
Westmead Hospital - Westmead
Recruitment hospital [3] 2239 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 2240 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 2241 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 2242 0
Concord Repatriation Hospital - Concord
Recruitment hospital [7] 2243 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 2244 0
Western Hospital - Footscray
Recruitment hospital [9] 2245 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [10] 2246 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 3694 0
Logan Hospital - Meadowbrook
Recruitment postcode(s) [1] 3126 0
2145
Recruitment postcode(s) [2] 3127 0
3168
Recruitment postcode(s) [3] 3128 0
3052
Recruitment postcode(s) [4] 3129 0
4102
Recruitment postcode(s) [5] 3130 0
5000
Recruitment postcode(s) [6] 3131 0
6009
Recruitment postcode(s) [7] 3132 0
2065
Recruitment postcode(s) [8] 9520 0
3021 - St Albans
Recruitment postcode(s) [9] 9521 0
3084 - Heidelberg
Recruitment postcode(s) [10] 9522 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [11] 9523 0
4131 - Meadowbrook
Recruitment outside Australia
Country [1] 2809 0
New Zealand
State/province [1] 2809 0
Otago

Funding & Sponsors
Funding source category [1] 257415 0
Commercial sector/Industry
Name [1] 257415 0
SHIRE PHARMACEUTICAL DEVELOPMENT LIMITED
Address [1] 257415 0
Hampshire International Business Park, Chineham, Basingstoke, Hampshire RG24 8EP
Country [1] 257415 0
United Kingdom
Funding source category [2] 291092 0
Government body
Name [2] 291092 0
NHMRC Project Grant
Address [2] 291092 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [2] 291092 0
Australia
Primary sponsor type
University
Name
Australasian Kidney Trials Network (University of Qld)
Address
St Lucia, Brisbane, QLD 4072
Country
Australia
Secondary sponsor category [1] 256648 0
None
Name [1] 256648 0
Address [1] 256648 0
Country [1] 256648 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259440 0
University of Queensland Human Research Ethics Committee
Ethics committee address [1] 259440 0
St Lucia, Brisbane, QLD 4072
Ethics committee country [1] 259440 0
Australia
Date submitted for ethics approval [1] 259440 0
01/11/2010
Approval date [1] 259440 0
16/11/2011
Ethics approval number [1] 259440 0

Summary
Brief summary
The main objective of the study is to determine whether use of a phosphate binder (lanthanum carbonate) in subjects with chronic kidney disease (CKD) stages 3b and 4 will reduce the risk and burden of cardiovascular disease. Patients with CKD 3b and 4 have a substantially higher incidence of cardiovascular disease contributing to significant morbidity and mortality. Phosphate imbalance is a putative non-traditional risk factor for cardiovascular disease in this population (association studies) and lowering of serum phosphate levels with a phosphate binder may be associated with reduced morbidity and mortality. The use of lanthanum carbonate to reduce phosphate and calcium-phosphate product may improve arterial compliance and attenuate the development and/or progression of vascular calcification, reduce the incidence of secondary hyperparathyroidism, and potentially reduce the rate of CKD progression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31490 0
Dr Genie Pedagogos
Address 31490 0
Epworth Eastern Hospital 1 Arnold Street Box Hill Vic 3128
Country 31490 0
Australia
Phone 31490 0
+61 417309472
Fax 31490 0
Email 31490 0
Genie.Pedagogos@epworth.org.au
Contact person for public queries
Name 14737 0
Miss Andrea Valks
Address 14737 0
Australasian Kidney Trials Network (UQ), Main Building 4th Floor, Princess Alexandra Hospital, 199 Ipswich Road, WOOLLOONGABBA QLD 4102
Country 14737 0
Australia
Phone 14737 0
+61 3443 7092
Fax 14737 0
+61 7 3103 4622
Email 14737 0
improve@uq.edu.au
Contact person for scientific queries
Name 5665 0
Dr Dr Nigel Toussaint
Address 5665 0
Monash Medical Centre
Department of Nephrology
246 Clayton Road,
(Locked Bag 29)
CLAYTON, Victoria, 3168
Country 5665 0
Australia
Phone 5665 0
+61 418 560 198
Fax 5665 0
Email 5665 0
nigel.toussaint@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in the primary publication, after deidentification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.
When will data be available (start and end dates)?
Beginning 2 years and ending 5 years following main publication.
Available to whom?
An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise.
Available for what types of analyses?
An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise. Proposals may be submitted up to 5 years following article publication. After 5 years, the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
How or where can data be obtained?
An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary