Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05374291
Registration number
NCT05374291
Ethics application status
Date submitted
22/04/2022
Date registered
16/05/2022
Date last updated
3/06/2024
Titles & IDs
Public title
The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD
Query!
Scientific title
A Randomized Controlled Clinical Trial to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe Chronic Kidney Disease
Query!
Secondary ID [1]
0
0
2021-005446-15
Query!
Secondary ID [2]
0
0
202100617
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Kidney Disease, Chronic
0
0
Query!
Renal Transplant Failure
0
0
Query!
Heart Failure
0
0
Query!
Kidney Failure
0
0
Query!
Death
0
0
Query!
Condition category
Condition code
Renal and Urogenital
0
0
0
0
Query!
Kidney disease
Query!
Renal and Urogenital
0
0
0
0
Query!
Other renal and urogenital disorders
Query!
Cardiovascular
0
0
0
0
Query!
Coronary heart disease
Query!
Cardiovascular
0
0
0
0
Query!
Other cardiovascular diseases
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Dapagliflozin 10 mg/day (oral)
Treatment: Drugs - Placebo
Experimental: Dapagliflozin - Dapagliflozin 10 mg/day (oral)
Placebo comparator: Placebo - Placebo 10 mg/day (oral)
Treatment: Drugs: Dapagliflozin 10 mg/day (oral)
Patients take 10 mg dapagliflozin or matching placebo once daily in the morning
Treatment: Drugs: Placebo
Patients take 10 mg dapagliflozin or matching placebo once daily in the morning
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of partipants with all-cause mortality, kidney failure, and hospitalization for heart failure
Query!
Assessment method [1]
0
0
To determine whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint
Combined endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure in the overall study population
Query!
Timepoint [1]
0
0
Total study duration intended to last 48 months
Query!
Secondary outcome [1]
0
0
Number of participants to reach all-cause mortality
Query!
Assessment method [1]
0
0
To determine if dapagliflozin is superior to placebo in reducing the incidence of all-cause mortality
Query!
Timepoint [1]
0
0
Total study duration intended to last 48 months
Query!
Secondary outcome [2]
0
0
Incidence of hospitalization for heart failure
Query!
Assessment method [2]
0
0
Incidence of hospitalization for heart failureTo determine if dapagliflozin is superior to placebo in reducing the incidence of heart failure
Query!
Timepoint [2]
0
0
Total study duration intended to last 48 months
Query!
Secondary outcome [3]
0
0
Incidence of kidney failure (chronic dialysis, kidney transplantation or mortality due to kidney failure)
Query!
Assessment method [3]
0
0
To determine if dapagliflozin is superior to placebo in reducing the incidence of kidney failure
Query!
Timepoint [3]
0
0
Total study duration intended to last 48 months
Query!
Secondary outcome [4]
0
0
incidence of the composite outcome (kidney failure, hospitalization for heart failure, and all-cause mortality) in subgroups
Query!
Assessment method [4]
0
0
To determine whether dapagliflozin is superior to placebo in reducing the incidence of the composite outcome in subgroups
subgroups: advanced CKD i.e. an eGFR =30 mL/min/1.73m2, dialysis patients and transplant patients
Query!
Timepoint [4]
0
0
Total study duration intended to last 48 months
Query!
Eligibility
Key inclusion criteria
* Patients with advanced CKD i.e. an eGFR =25 mL/min/1.73m2
* Dialysis patients (at least 3 months after start of dialysis)
* Transplant patients with an eGFR =45 mL/min/1.73m2 (at least 6 months after transplantation)
In addition, to be eligible all subjects must meet all criteria below
* Age >18 years
* Willing to sign informed consent
* Pre-dialysis patients with eGFR =25 mL/min/1.73m2 have to be on a stable dose (no changes in dose or type of drug) of ACEis or ARBs for at least 4 weeks prior to the screening visit to be eligible to proceed to the randomization visit unless there is documented evidence that the patient does not tolerate an ACEi or ARB. These subjects will maintain their stable doses of ACEis or ARBs throughout the trial (when possible and tolerated by the patient). ACEi or ARBs are not required for patients on maintenance dialysis or kidney transplant recipients.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Mentally incapacitated subjects (i.e. not able to sign informed consent)
* Diagnosis of type 1 diabetes mellitus
* Concurrent treatment with SGLT2 inhibitor
* History of =2 urinary tract / genital infections during the last six months
* Life expectancy <6 months in the opinion of the treating physician.
* Scheduled start of dialysis within 3 months or kidney transplantation within 6 months
* patients treated for a renal indication during the last 6 months with a course of systemic immunosuppressive agents or intensification of treatment with systemic immunosuppressive agents, such as patients with a kidney transplant and acute rejection or patients with GPA (Morbus Wegener) and a recent flare.
* Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
* History of severe hypersensitivity or known severe hepatic impairment (Child-Pugh class C)
* History of severe noncompliance to medical regimens or unwillingness to comply with the study protocol.
* Pregnancy or breastfeeding
* Presence of other transplanted organ besides a kidney transplant
* Severe lactose intolerance
* Autosomal Dominant Polycystic Kidney Disease (ADPKD) treated with tolvaptan
Query!
Study design
Purpose of the study
Prevention
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
8/11/2022
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/01/2027
Query!
Actual
Query!
Sample size
Target
1500
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
Australian Capital TeritoryNSW,QLD,SA,VIC,WA
Query!
Recruitment hospital [1]
0
0
Canberra Health Services - Canberra
Query!
Recruitment hospital [2]
0
0
Concord Repatriation General Hospital - Sydney
Query!
Recruitment hospital [3]
0
0
Liverpool Hospital - Sydney
Query!
Recruitment hospital [4]
0
0
Prince of Wales Hospital - Sydney
Query!
Recruitment hospital [5]
0
0
Royal North Shore Hospital - Sydney
Query!
Recruitment hospital [6]
0
0
Royal Prince Alfred Hospital - Sydney
Query!
Recruitment hospital [7]
0
0
St George Hospital - Sydney
Query!
Recruitment hospital [8]
0
0
Westmead Hospital - Sydney
Query!
Recruitment hospital [9]
0
0
Wollongong Hospital - Wollongong
Query!
Recruitment hospital [10]
0
0
Sunshine Coast Hospital and Health Services - Birtinya
Query!
Recruitment hospital [11]
0
0
Royal Brisbane and Womens Hospital - Brisbane
Query!
Recruitment hospital [12]
0
0
Townsville University hospital - Douglas
Query!
Recruitment hospital [13]
0
0
Royal Adelaide Hospital - Adelaide
Query!
Recruitment hospital [14]
0
0
Western Health - Melbourne
Query!
Recruitment hospital [15]
0
0
Royal Melbourne Hospital - Parkville
Query!
Recruitment hospital [16]
0
0
East Metro Health Services (Royal Perth Hospital and Armadale Health Services) - Perth
Query!
Recruitment hospital [17]
0
0
Box Hill Hospital (Eastern Health) - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
- Canberra
Query!
Recruitment postcode(s) [2]
0
0
- Sydney
Query!
Recruitment postcode(s) [3]
0
0
- Wollongong
Query!
Recruitment postcode(s) [4]
0
0
- Birtinya
Query!
Recruitment postcode(s) [5]
0
0
- Brisbane
Query!
Recruitment postcode(s) [6]
0
0
- Douglas
Query!
Recruitment postcode(s) [7]
0
0
- Adelaide
Query!
Recruitment postcode(s) [8]
0
0
- Melbourne
Query!
Recruitment postcode(s) [9]
0
0
- Parkville
Query!
Recruitment postcode(s) [10]
0
0
- Perth
Query!
Recruitment outside Australia
Country [1]
0
0
Germany
Query!
State/province [1]
0
0
Berlin
Query!
Country [2]
0
0
Germany
Query!
State/province [2]
0
0
Düsseldorf
Query!
Country [3]
0
0
Germany
Query!
State/province [3]
0
0
Erlangen
Query!
Country [4]
0
0
Germany
Query!
State/province [4]
0
0
Halle
Query!
Country [5]
0
0
Germany
Query!
State/province [5]
0
0
Hannover
Query!
Country [6]
0
0
Germany
Query!
State/province [6]
0
0
Heidelberg
Query!
Country [7]
0
0
Germany
Query!
State/province [7]
0
0
Heilbronn
Query!
Country [8]
0
0
Germany
Query!
State/province [8]
0
0
Jena
Query!
Country [9]
0
0
Germany
Query!
State/province [9]
0
0
Mainz
Query!
Country [10]
0
0
Germany
Query!
State/province [10]
0
0
Regensburg
Query!
Country [11]
0
0
Germany
Query!
State/province [11]
0
0
Tübingen
Query!
Country [12]
0
0
Germany
Query!
State/province [12]
0
0
Ulm
Query!
Country [13]
0
0
Germany
Query!
State/province [13]
0
0
Villingen-Schwenningen
Query!
Country [14]
0
0
Germany
Query!
State/province [14]
0
0
Wiesbaden
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Würzburg
Query!
Country [16]
0
0
Netherlands
Query!
State/province [16]
0
0
Noord-brabant
Query!
Country [17]
0
0
Netherlands
Query!
State/province [17]
0
0
Noord-Holland
Query!
Country [18]
0
0
Netherlands
Query!
State/province [18]
0
0
Zuid-Holland
Query!
Country [19]
0
0
Netherlands
Query!
State/province [19]
0
0
Alkmaar
Query!
Country [20]
0
0
Netherlands
Query!
State/province [20]
0
0
Amersfoort
Query!
Country [21]
0
0
Netherlands
Query!
State/province [21]
0
0
Amstelveen
Query!
Country [22]
0
0
Netherlands
Query!
State/province [22]
0
0
Amsterdam
Query!
Country [23]
0
0
Netherlands
Query!
State/province [23]
0
0
Apeldoorn
Query!
Country [24]
0
0
Netherlands
Query!
State/province [24]
0
0
Delft
Query!
Country [25]
0
0
Netherlands
Query!
State/province [25]
0
0
Den Bosch
Query!
Country [26]
0
0
Netherlands
Query!
State/province [26]
0
0
Deventer
Query!
Country [27]
0
0
Netherlands
Query!
State/province [27]
0
0
Eindhoven
Query!
Country [28]
0
0
Netherlands
Query!
State/province [28]
0
0
Groningen
Query!
Country [29]
0
0
Netherlands
Query!
State/province [29]
0
0
Hilversum
Query!
Country [30]
0
0
Netherlands
Query!
State/province [30]
0
0
Hoofddorp
Query!
Country [31]
0
0
Netherlands
Query!
State/province [31]
0
0
Kerkrade
Query!
Country [32]
0
0
Netherlands
Query!
State/province [32]
0
0
Leeuwarden
Query!
Country [33]
0
0
Netherlands
Query!
State/province [33]
0
0
Leiden
Query!
Country [34]
0
0
Netherlands
Query!
State/province [34]
0
0
Lelystad
Query!
Country [35]
0
0
Netherlands
Query!
State/province [35]
0
0
Maastricht
Query!
Country [36]
0
0
Netherlands
Query!
State/province [36]
0
0
Nieuwegein
Query!
Country [37]
0
0
Netherlands
Query!
State/province [37]
0
0
Nijmegen
Query!
Country [38]
0
0
Netherlands
Query!
State/province [38]
0
0
Roosendaal
Query!
Country [39]
0
0
Netherlands
Query!
State/province [39]
0
0
Rotterdam
Query!
Country [40]
0
0
Netherlands
Query!
State/province [40]
0
0
Uden
Query!
Country [41]
0
0
Netherlands
Query!
State/province [41]
0
0
Utrecht
Query!
Country [42]
0
0
Netherlands
Query!
State/province [42]
0
0
Venlo
Query!
Country [43]
0
0
Netherlands
Query!
State/province [43]
0
0
Zwolle
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
University Medical Center Groningen
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/industry
Query!
Name [1]
0
0
AstraZeneca
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Other collaborator category [2]
0
0
Other
Query!
Name [2]
0
0
Dutch Kidney Foundation
Query!
Address [2]
0
0
Query!
Country [2]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
Rationale: Sodium glucose co transporter 2 (SGLT2) inhibitors are a relatively new class of agents, originally developed as oral antihyperglycemic drugs. SGLT2 inhibitors are clinically available since 2012 for the treatment of patients with diabetes mellitus type 2. Later, SGLT2 inhibitors appeared to have also specific reno- and cardioprotective effects. Remarkably, the trials that have been performed thus far excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. This is unfortunate, because especially these patients are at high risk of reaching kidney failure requiring dialysis, cardiovascular complications and mortality, whereas there are only few proven effective therapies. There is emerging evidence from experimental studies and post hoc-analyses of randomized clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in these patients with severe CKD, including patients receiving dialysis or living with a kidney transplant. For instance, subgroup analysis of the DAPA-CKD trial comparing 624 patients with an eGFR\<30 to the remainder of the trial population with better kidney function, demonstrated that the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiovascular, heart failure and renal outcomes persisted in the population with impaired kidney function. Furthermore, in the DAPA-CKD trial patients continued to use dapagliflozin or placebo when dialysis was initiated. In the subgroup of patients who initiated dialysis, dapagliflozin was associated with a relative risk reduction for mortality of 21%. Finally, in kidney transplant recipients, SGLT2 inhibitors have been shown to be effective in lowering HbA1c, body weight, blood pressure and stabilize kidney function, and these agents were well tolerated and safe. Taken these findings together there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD. There are two cardiac sub-studies: the cardiac MRI substudy and the echocardiography sub-study. The echocardiography sub-study is referred to as the "SGLT-2-inhibitors to Target Heart Failure in Peritoneal Dialysis" (STOP HF in PD) study. In STOP HF in PD the effect of dapagliflozin on cardiac function will be assessed in a subset of 100 patients treated with peritoneal dialysis.
Query!
Trial website
https://clinicaltrials.gov/study/NCT05374291
Query!
Trial related presentations / publications
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14. Heerspink HJL, Jongs N, Chertow GM, Langkilde AM, McMurray JJV, Correa-Rotter R, Rossing P, Sjostrom CD, Stefansson BV, Toto RD, Wheeler DC, Greene T; DAPA-CKD Trial Committees and Investigators. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 Nov;9(11):743-754. doi: 10.1016/S2213-8587(21)00242-4. Epub 2021 Oct 4. Erratum In: Lancet Diabetes Endocrinol. 2022 Oct;10(10):e10. doi: 10.1016/S2213-8587(22)00223-6. Chertow GM, Vart P, Jongs N, Toto RD, Gorriz JL, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Sjostrom CD, Stefansson BV, Langkilde AM, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. J Am Soc Nephrol. 2021 Sep;32(9):2352-2361. doi: 10.1681/ASN.2021020167. Epub 2021 Jul 16. Chewcharat A, Prasitlumkum N, Thongprayoon C, Bathini T, Medaura J, Vallabhajosyula S, Cheungpasitporn W. Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis. Med Sci (Basel). 2020 Nov 17;8(4):47. doi: 10.3390/medsci8040047.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Ron Gansevoort
Query!
Address
0
0
University Medical Center Groningen
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
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
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05374291
Download to PDF