This study has been transitioned to CTIS with ID 2023-508389-13-00 check the CTIS register for the current data. To determine whether dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint of kidney failure…
ID
Source
Brief title
Condition
- Other condition
- Nephropathies
Synonym
Health condition
Hemo- and peritoneal dialysis patients; Transplant patients
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the incidence of a composite of all-cause
mortality, kidney failure, and heart failure hospitalization. This is a
clinically relevant outcome measure and previous trials with dapagliflozin in
patients with earlier stages of CKD than enrolled in the current trial have
shown that dapaglilflozin reduces the incidence of each of these outcomes.
Secondary outcome
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)
• 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 with residual diuresis >=500 mL/24h
• Transplant patients with an eGFR <=45 mL/min/1.73m2
Background summary
Chronic kidney disease (CKD) affects approximately 10% of the adult population
worldwide. The most common causes of CKD are diabetes, hypertension, and
chronic glomerulonephritis. Subjects with CKD are at high risk for various
complications, among others cardiovascular morbidity and mortality, heart
failure, and end-stage kidney disease requiring kidney replacement
therapy.Treatment for CKD encompasses tight blood pressure control, preferably
with angiotensin converting enzyme inhibitor (ACE-I) or angiotensin II receptor
blockers (ARBs) as well as a tight glucose control in diabetic patients to
prevent or delay progression of CKD and CVD. These interventions have been
proven efficacious, but still the residual risk to develop cardiovascular
complications and to reach kidney failure remains high. There is therefore a
need for additional interventions.
Study objective
This study has been transitioned to CTIS with ID 2023-508389-13-00 check the CTIS register for the current data.
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 with
residual diuresis >= 500 mL/24hr , and kidney transplant recipients with eGFR
<=45 mL/min/1.73m2.
Study design
This is a randomized, double-blind, parallel-group study
Intervention
Dapagliflozine 10mg/dag vs placebo
Study burden and risks
The study population chosen for this study is a broad population of patients
with severe CKD. Three patient groups will be included: patients with an eGFR
<=25 ml/min/1.73 m2 (not on dialysis or undergoing a kidney transplant); common
dialysis patients with residual diuresis >=500 ml/24 hours (including hemo- and
peritoneal dialysis), and recipients of kidney transplants. These patients are
almost always excluded from clinical trials, while they are at very high risk
of adverse outcomes and few effective therapies are available for these
patients. Phase 2/3 clinical trials have also shown that dapagliflozin reduces
albuminuria, an important risk marker for renal and cardiovascular disease
progression.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
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 with a residual diuresis >=500 mL/24h
(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.
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 scheduled kidney
transplantation within 6 months
• In patients with an eGFR <=25 mL/min/1.73m2: kidney disease treated with
immunosuppressive agents during the last 6 months
• patients treated during the last 6 months with a course of immunosuppressive
agents or intensification of treatment with 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.
• Current pregnancy, lactation or women of child-bearing potential
(WOCBP) unless using highly-effective contraceptive
measurements until 4 weeks after last intake of the study medication
• Presence of other transplanted organ besides a kidney transplant
• Severe lactose intolerance
• Autosomal Dominant Polycystic Kidney Disease (ADPKD) treated with
tolvaptan
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508389-13-00 |
| EudraCT | EUCTR2021-005446-15-NL |
| ClinicalTrials.gov | NCT05374291 |
| CCMO | NL80581.042.22 |