Demonstrate whether, in addition to standard of care (SoC), finerenone is superior to placebo in delaying the progression of kidney disease, as measured by the composite endpoint of time to first occurrence of kidney failure, a sustained decrease of…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to:
Demonstrate whether, in addition to standard of care (SoC), finerenone is
superior to placebo in delaying the progression of kidney disease, as measured
by the composite endpoint of time to first occurrence of kidney failure, a
sustained decrease of eGFR * 40% from baseline over at least 4 weeks or renal
death.
Secondary outcome
The secondary objectives of this study are to determine whether finerenone, in
addition to SoC, compared to placebo:
- Delays the time to first occurrence of the following composite endpoint: CV
death or non-fatal CV events (i.e. non-fatal myocardial infarction, non-fatal
stroke, hospitalization for heart failure)
- Delays the time to all-cause mortality
- Delays the time to all-cause hospitalization
- Change in urinary albumin-to-creeatine ratio (UCAR) from baseline to month 4
- Time to first occurrence of the following composite endpoint: onset of kidney
failure, a sustained decrease in estimated glomerular filtration rate
Background summary
Individuals with diabetic kidney disease (DKD) are at elevated risk of
cardiovascular morbidity and mortality, as well as progression of kidney
disease. An inappropriate release of aldosterone contributes to the target
organ damage found in conditions such as heart failure, chronic kidney disease
and hypertension. Blockade of the action of aldosterone has demonstrated
benefit in different forms of cardiovascular disease. Results from short-term
studies show that treatment with mineralocorticoid receptor antagonists in
addition to renin-angiotensin system (RAS) blockade improves albuminuria, but
long-term outcome studies are lacking.
Finerenone, a potent and selective mineralocorticoid receptor blocker, is
proposed to address the unmet medical needs in the DKD population, by providing
protection against the development or recurrence of cardiovascular disease, as
well as the progression of kidney disease, when added to current standard of
care therapy with a RAS inhibitor.
Study objective
Demonstrate whether, in addition to standard of care (SoC), finerenone is
superior to placebo in delaying the progression of kidney disease, as measured
by the composite endpoint of time to first occurrence of kidney failure, a
sustained decrease of eGFR * 40% from baseline over at least 4 weeks or renal
death.
Study design
A randomized, double-blind, placebo-controlled, parallel-group, multicenter,
event-driven study
Intervention
10 mg or 20 mg finerenone once a day (depending on the eGFR ) compared to a
placebo .
Study burden and risks
Two screening visits, and up to 4 study visits in the first 6 months and
thereafter visits every 4 months until the end of the study
Blood samples at each study visit.
Urine sample collection at specific visits (3 samples collected over 3 days)
Two questionnaires to complete at specific visits. EQ- 5D-5L - 2 pages in
length and KDQL consists of 36 questions.
Physical Examination at specific visits.
ECG assessment at specific visits.
Some patients may need to modify current medication before entering the study.
Finerenone may have some therapeutic benefit, however this cannot be
guaranteed. Patients are at risk of experiencing side effects.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
- Men or women aged 18 years and older. The lower age limit may be higher if legally required in the participating country.
- Women of childbearing potential can only be included in the study if a pregnancy test is negative at the Screening Visit and if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy.
- Subjects with type 2 diabetes mellitus as defined by the American Diabetes Association
- Subjects with a clinical diagnosis of DKD based on either of the following criteria at the Run-in and Screening Visit:
* Persistent high albuminuria defined as UACR of * 30 mg/g ( * 3.4 mg/mmol) but < 300 mg/g (< 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR * 25 but < 60 mL/min/1.73 m2 and presence of diabetic retinopathy in the medical history
OR
* Persistent very high albuminuria defined as UACR of * 300 mg/g (* 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR * 25 but < 75 mL/min/1.73 m2
- Prior treatment with ACEIs and ARBs as follows:
* For at least 4 weeks prior to the Run-in Visit, subjects should be treated with either an ACEI or ARB, or both
* Starting with the Run in Visit, subjects should be treated with only an ACEI or ARB
* For at least 4 weeks prior to the Screening Visit, subjects should be treated with the maximum tolerated labeled dose (but not below the minimal labeled dose) of only an ACEI or an ARB (not both) preferably without any adjustments to dose or choice of agent or to any other antihypertensive or antiglycemic treatment
- Serum potassium * 4.8 mmol/L at both the Run-in and the Screening Visit
Exclusion criteria
- Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis
- HbA1c >12% (> 108 mmol/mol) at the Run-in Visit or Screening Visit
- Uncontrolled arterial hypertension with mean sitting systolic blood pressure (SBP) * 170 mmHg or mean sitting diastolic blood pressure (DBP) * 110 mmHg at the Run in Visit or mean sitting SBP * 160 mmHg or mean sitting DBP * 100 mmHg at the Screening Visit
- Subjects with a clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the Run in Visit (class 1A recommendation for MRAs)
- Dialysis for acute renal failure within 12 weeks prior to the Run-in Visit
- Renal allograft in place or a scheduled kidney transplant within the next 12 months from the Run in Visit
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 |
|---|---|
| EudraCT | EUCTR2015-000990-11-NL |
| CCMO | NL54196.015.15 |