ANZCTR - Registration

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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

3/06/2024

Date data sharing statement initially provided

5/02/2019

Date results provided

29/06/2021

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]

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

Condition category

Condition code

Renal and Urogenital

Kidney disease

Cardiovascular

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]

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]

Arterial compliance (measured by pulse wave velocity) as a surrogate marker of cardiovascular morbidity and mortality

Timepoint [1]

At baseline and at 6 months, 12 months, 18 months and 24 months post randomisation

Secondary outcome [1]

Aortic calcification measured with Computed Tomography (CT)

Timepoint [1]

At baseline and 24 months post randomisation.

Secondary outcome [2]

Serum Phospate, Calcium, calcium phosphate product and parathyroid hormone levels

Timepoint [2]

At baseline and at 3, 6, 9, 12, 15, 18, 21, and 24 months post randomisation

Secondary outcome [3]

renal function, measured by estimated Glomerular Filtration Rate (eGFR) and % change

Timepoint [3]

At baseline and at 12 months and 24 months post randomisation

Secondary outcome [4]

Bone mineral density, measured by CT of the lumbar spine

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/11/2011

Actual

19/03/2012

Date of last participant enrolment

Anticipated

31/12/2016

Actual

20/01/2017

Date of last data collection

Anticipated

3/12/2018

Actual

27/12/2018

Sample size

Target

488

Accrual to date

Final

278

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [2]

Westmead Hospital - Westmead

Recruitment hospital [3]

Royal North Shore Hospital - St Leonards

Recruitment hospital [4]

Flinders Medical Centre - Bedford Park

Recruitment hospital [5]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [6]

Concord Repatriation Hospital - Concord

Recruitment hospital [7]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [8]

Western Hospital - Footscray

Recruitment hospital [9]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [10]

Royal North Shore Hospital - St Leonards

Recruitment hospital [11]

Logan Hospital - Meadowbrook

Recruitment postcode(s) [1]

2145

Recruitment postcode(s) [2]

3168

Recruitment postcode(s) [3]

3052

Recruitment postcode(s) [4]

4102

Recruitment postcode(s) [5]

5000

Recruitment postcode(s) [6]

6009

Recruitment postcode(s) [7]

2065

Recruitment postcode(s) [8]

3021 - St Albans

Recruitment postcode(s) [9]

3084 - Heidelberg

Recruitment postcode(s) [10]

2065 - Royal North Shore Hospital

Recruitment postcode(s) [11]

4131 - Meadowbrook

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Otago

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

SHIRE PHARMACEUTICAL DEVELOPMENT LIMITED

Address [1]

Hampshire International Business Park, Chineham, Basingstoke, Hampshire RG24 8EP

Country [1]

United Kingdom

Funding source category [2]

Government body

Name [2]

NHMRC Project Grant

Address [2]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [2]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Queensland Human Research Ethics Committee

Ethics committee address [1]

St Lucia, Brisbane, QLD 4072

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/11/2010

Approval date [1]

16/11/2011

Ethics approval number [1]

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

10.1159/000505717

Public notes

Contacts

Principal investigator

Name

Dr Genie Pedagogos

Address

Epworth Eastern Hospital 1 Arnold Street Box Hill Vic 3128

Country

Australia

Phone

+61 417309472

Fax

[email protected]

Contact person for public queries

Name

Andrea Valks

Address

Australasian Kidney Trials Network (UQ), Main Building 4th Floor, Princess Alexandra Hospital, 199 Ipswich Road, WOOLLOONGABBA QLD 4102

Country

Australia

Phone

+61 3443 7092

Fax

+61 7 3103 4622

[email protected]

Contact person for scientific queries

Name

Nigel Toussaint

Address

Monash Medical Centre
Department of Nephrology
246 Clayton Road,
(Locked Bag 29)
CLAYTON, Victoria, 3168

Country

Australia

Phone

+61 418 560 198

Fax

[email protected]

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?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
12350	Study protocol		https://aktn.org.au
12351	Statistical analysis plan		https://aktn.org.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction on Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study.	2019	https://dx.doi.org/10.1136/bmjopen-2018-024382
Embase	A randomized trial on the effect of phosphate reduction on vascular end points in CKD (improve-CKD).	2020	https://dx.doi.org/10.1681/ASN.2020040411
Embase	Aortic Calcification and Arterial Stiffness Burden in a Chronic Kidney Disease Cohort with High Cardiovascular Risk: Baseline Characteristics of the Impact of Phosphate Reduction On Vascular End-Points in Chronic Kidney Disease Trial.	2020	https://dx.doi.org/10.1159/000505717
Dimensions AI	Dietary Phosphate Consumption in Australians With Stages 3b and 4 Chronic Kidney Disease	2020	https://doi.org/10.1053/j.jrn.2020.02.007
Embase	Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD - results from a placebo-controlled randomized trial.	2023	https://dx.doi.org/10.1093/ndt/gfac043

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically