Clinical trial NCT01345656: BAY94-8862 Dose Finding Trial in Subjects With Chronic Heart Failure and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease
Official title: A Randomized, Double-blind, Multi-center Study to Assess Safety and Tolerability of Different Oral Doses of BAY94-8862 in Subjects With Stable Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease Versus Placebo (Part A) or Versus Placebo and Spironolactone (Part B)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Chronic Heart Failure
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-05-02
Enrollment: 457
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A placebo (Part A) and placebo and active comparator controlled (Part B), double-blind and randomized study to assess safety and tolerability of a new drug (BAY94-8862) given orally


Eligibility criteria: Inclusion Criteria:

* Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy
* Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated
* Known kidney damage for \>/= 3 months, as defined by structural or functional abnormalities of the kidney, and

  * Part A: 60 mL/min/1.73 m\*2 \</= eGFR (estimated Glomerular Filtration Rate) \< 90 mL/min/1.73 m\*2 (MDRD, Modification of Diet in Renal Disease) at the screening visit
  * Part B: 30 mL/min/1.73 m\*2 \</= eGFR \<= 60 mL/min/1.73 m\*2 (MDRD) at the screening visit
* Serum potassium \</= 4.8 mmol/L at the screening visit
* Systolic blood pressure \>/= 90 mmHg without signs or symptoms of hypotension at the screening visit

Exclusion Criteria:

* Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only)
* Subjects with anuria, acute renal failure, or Addison's disease
* Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization
* Valvular heart disease requiring surgical intervention during the course of the study
* History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment

Primary outcomes:
measure: Change of serum potassium
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in serum magnesium
timeFrame: Day 8, Day 15, Day 22, Day 29
measure: Change in blood pressure
timeFrame: Day 8, Day 15, Day 22, Day 29
measure: Change in heart rate
timeFrame: Day 8, Day 15, Day 22, Day 29
Other outcomes:
Locations:
city: Linz
country: Austria
state: Oberösterreich
city: Graz
country: Austria
state: Steiermark
city: Wien
country: Austria
city: Brasschaat
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Roeselare
country: Belgium
city: Brno
country: Czechia
city: Liberec
country: Czechia
city: Praha 2
country: Czechia
city: Praha 5
country: Czechia
city: Copenhagen Ø
country: Denmark
city: Esbjerg
country: Denmark
city: Frederiksberg
country: Denmark
city: Hellerup
country: Denmark
city: Herlev
country: Denmark
city: Hvidovre
country: Denmark
city: København NV
country: Denmark
city: Køge
country: Denmark
city: Odense
country: Denmark
city: Svendborg
country: Denmark
city: Viborg
country: Denmark
city: Helsinki
country: Finland
city: Jyväskylä
country: Finland
city: Turku
country: Finland
city: Frankfurt
country: Germany
state: Hessen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Wermsdorf
country: Germany
state: Sachsen
city: Wedel
country: Germany
state: Schleswig-Holstein
city: Erfurt
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Hadera
country: Israel
city: Petah Tikva
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Zefat
country: Israel
city: Oslo
country: Norway
city: Stavanger
country: Norway
city: Krakow
country: Poland
city: Piotrkow Trybunalski
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Kristianstad
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Pitt B, Filippatos G, Gheorghiade M, Kober L, Krum H, Ponikowski P, Nowack C, Kolkhof P, Kim SY, Zannad F. Rationale and design of ARTS: a randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012 Jun;14(6):668-75. doi: 10.1093/eurjhf/hfs061. Epub 2012 May 4.
citation: Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013 Aug;34(31):2453-63. doi: 10.1093/eurheartj/eht187. Epub 2013 May 27.
citation: Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.