Renal Lifecycle Trial: A Randomized Controlled Clinical Trial to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients with Severe Chronic Kidney Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

8 Nov 2022 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca · Dutch Kidney Foundation

External identifiers

EU CT number

2023-508389-13-00

EudraCT number

2021-005446-15

ClinicalTrials.gov

NCT05374291

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy, Safety

To determine whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint of kidney failure, hospitalization for heart failure, and all-cause mortality in the overall patient group, consisting of patients with eGFR ≤25 mL/min/1.73m2, dialysis patients, and kidney transplant recipients with eGFR ≤45 mL/min/1.73m2.

Secondary objectives 2

1. To determine if dapagliflozin is superior to placebo in reducing the incidence of each of the components of the primary composite endpoint in the overall patient group: All-cause mortality Kidney failure (chronic dialysis, kidney transplantation or mortality due to kidney failure)1 Hospitalization for heart failure
2. to determine whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint of all-cause mortality, kidney failure, or heart failure hospitalization in each of the three subgroups of patients: Patients with advanced CKD i.e. an eGFR ≤25 mL/min/1.73m2; dialysis patients; transplant patients with an eGFR ≤45mL/min/1.73m2

Conditions and MedDRA coding

Combined endpoint of all-cause mortality, kidney failure, and hospitalization for heart failure in the overall study population

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. In order to be eligible to participate in the randomized controlled double blind trial subject must meet the criteria for one of the three strata: Patients with advanced CKD i.e. an eGFR ≤25 mL/min/1.73m2; Hemo- and peritoneal 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)
2. Age ≥18 years
3. Willing to sign informed consent
4. 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.

Exclusion criteria 14

1. Mentally incapacitated subjects (i.e. not able to sign informed consent)
2. Diagnosis of type 1 diabetes mellitus
3. Concurrent treatment with SGLT2 inhibitor
4. History of ≥2 urinary tract / genital infections during the last six months
5. Life expectancy <6 months in the opinion of the treating physician.
6. Scheduled start of dialysis within 3 months or scheduled kidney transplantation within 6 months
7. 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. Of note, this implies that patients receiving non-systemic immunosuppression (e.g. topical, ophthalmic, rectal, intra-articular or inhaled corticosteroids) are allowed to participate, as well as patients having received a short course of oral/IV steroids within 6 months prior to screening for non-renal indications (e.g. for gout or an asthma flare) as well as patients receiving during the last 6 months stable low-dose immunosuppression for whatever reason (e.g. kidney transplant recipients, patients with GPA, patients with gout).
8. Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
9. History of severe hypersensitivity or known severe hepatic impairment (Child-Pugh class C)
10. History of severe noncompliance to medical regimens or unwillingness to comply with the study protocol.
11. Current pregnancy, lactation or women of child-bearing potential (WOCBP) unless using highly-effective contraceptive measurements7 until 4 weeks after last intake of the study medication
12. Presence of other transplanted organ besides a kidney transplant
13. Severe lactose intolerance (of note: The study medication contains so little lactose that most people with lactose intolerance do not suffer from this.)
14. Autosomal Dominant Polycystic Kidney Disease (ADPKD) treated with tolvaptan

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to the composite endpoint of all-cause mortality, kidney failure (chronic dialysis, kidney transplantation or death due to kidney failure), and hospitalization for heart failure

Secondary endpoints 4

1. Time to kidney failure (in advanced CKD and transplant patients only)
2. Time to the first occurrence of heart failure hospitalization
3. Time to all-cause death
4. In addition, it will be investigated whether dapagliflozin is superior to placebo in reducing the incidence of the composite outcome of all-cause mortality, kidney failure, or heart failure hospitalization in each of the three subpopulations.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Ron Gansevoort

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Ron Gansevoort

Locations

4 EU/EEA countries · 93 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications