Placebo controlled, randomized, double-blind, multi-center, multinational Phase IIb study to investigate the efficacy and tolerability of BAY 58-2667 given intravenously in patients with acute decompensated chronic congestive heart failure

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-003059-36-LT
• Date of registration: 29/10/2007
• Prospective Registration: Yes
• Primary sponsor: Bayer Healthcare AG
• Public title: Placebo controlled, randomized, double-blind, multi-center, multinational Phase IIb study to investigate the efficacy and tolerability of BAY 58-2667 given intravenously in patients with acute decompensated chronic congestive heart failure
• Scientific title: Placebo controlled, randomized, double-blind, multi-center, multinational Phase IIb study to investigate the efficacy and tolerability of BAY 58-2667 given intravenously in patients with acute decompensated chronic congestive heart failure
• Date of first enrolment: 10/12/2007
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003059-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Estonia, Germany, Hungary, Italy, Lithuania, Poland, Slovenia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
The following inclusion criteria must be met:

• Patients with acute decompensated chronic congestive heart failure, NYHA functional class III-IV, either ischemic or non-ischemic, requiring hospitalization, and with clinical indication for parenteral pharmacotherapy and invasive hemodynamic monitoring (i.e indwelling Swan-Ganz pulmonary artery catheter) and PCWP = 18 mmgHg.

• Patients must have the clinical diagnosis of CHF made at least 3 month prior to enrollment.

• Male or female patients, aged 18 years or more. Female patients should be postmenopausal for at least one year.

• Patients must experience worsening of at least one of the symptoms below leading to hospitalization at the time of entry into the study:
Dyspnea Symptoms such as:
Dyspnea (labored or difficult breathing) at rest,
Dyspnea (labored or difficult breathing) on minimal exertion
Orthopnea (difficult breathing except in the upright position),
Nocturnal dyspnea (awaken from sleep due to respiratory distress).
or
Clinical evidence of volume overload such as:
peripheral edema,
hepatic congestion with ascites,
pulmonary congestion/rales, or pleural effusion (chest X-ray)
jugular venous distension.

• Left ventricular ejection fraction < 40 % within the last 6 months.

• Ability to understand and willing to sign informed consent form.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The following factors determined during the run-in period will automatically exclude the subject from participating in the trial:
• Females of child-bearing potential.
• Acute de-novo heart failure.
• Acute myocardial infarction and/or myocardial infarction within 30 days.
• Valvular heart disease requiring surgical intervention during the course of the study.
• Heart failure due to or associated with uncorrected primary valvular disease, malfunctioning artificial heart valve, or uncorrected congenital heart disease.
• Primary hypertrophic cardiomyopathy.
• Acute inflammatory heart disease, e.g. acute myocarditis.
• Unstable angina requiring angiography
• Cardiogenic shock
• Patients requiring any of the following: : nitrates,( e.g. nitroprusside, nitroglycerin); vasodilators (e.g. nesiritide), any intravenous positive inotropic drug (e.g. levosimendan) or vasoconstrictive agents (e.g. catecholamines) within the last 3 hours (dobutamine up to 4 µg/kg/minute is allowed).
• Need for endotracheal intubation and mechanical ventilation.
• Patients with cardiac arrest or patients with history of cardiac arrest within 3 months, unless precipitated by an event such as an acute myocardial infarction, induction by catheter placement, severe transient electrolyte abnormality, an electrophysiology procedure, or addressed by automatic implantable cardioverter defibrillator placement.
• Patients with increased risk of cardiac arrest (e.g. AV Block °III, QTc > 450 msec for men and QTc > 470 msec for women if patient is in sinus rhythm and there is no conduction delay in the ECG influencing the QT-interval.)
• Ventricular fibrillation within 30 days (> 15 seconds long)
• Patients showing during ECG monitoring uncontrolled ventricular rhythm disorder.
• Uncontrolled atrial fibrillation or flutter or any supraventricular tachycardia.
• Cardiac surgery within the last month (such as cardiac revascularization surgery, valvular surgery, biventricular resynchronization procedure, ventricular reduction surgery or cardiac myoplasty, implantation of mechanical ventricular assist device).
• Systolic blood pressure < 100 mmHg or > 180 mmHg.
• Heart rate = 120 BPM
• Pulmonary embolism within the last 30 days prior to enrollment.
• PDE 5 inhibitor use within the last 48 hours.
• Strong CYP2C8 (inhibitors like gemfibrozil(stop at least 24 hours before study drug infusion)
• Heart failure secondary to pulmonary disease and patients with primary pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
• History of or clinically significant evidence of any severe disease other than heart failure that preclude participation.
• Known significant liver disease (e.g. acute clinical hepatitis, chronic active hepatitis, cirrhosis).
• Calculated creatinine clearance < 30 mL/min. using MDRD or Cockroft Gault equation
• BMI < 20 kg/m2 (BMI equal to 20 is accepted)
• Drug- or alcohol abuse.
• Concomitant participation in another trial or study.
• Therapy with another investigational product within 30 days prior start of study
• Any other condition or therapy, which in the opinion of the Principal Investigator would make the patient unsuitable for this study and presumably will not allow participation for the full planned study period.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with acute decompensated chronic congested heart failure
MedDRA version: 9.1 Level: LLT Classification code 10064653 Term: Acute decompensated heart failure

Intervention(s)

Product Name: BAY 58-2667
Product Code: BAY 58-2667
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: cinaciguat
CAS Number: 329773-35-5
Current Sponsor code: BAY 58-2667
Concentration unit: % (V/V) percent volume/volume
Concentration type: equal
Concentration number: 0.005-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Primary objective of the study is to investigate the safety and efficacy of a titration phase (8 hours) and a maintenance phase (maximum 40 hours) of intravenous BAY 58-2667 in patients with acute decompensated chronic congestive heart failure with the need for parenteral pharmacotherapy and invasive haemodynamic monitoring (i.e. indwelling Swan-Ganz pulmonary artery catheter) and PCWP = 18mmHg.

Primary end point(s): The primary efficacy outcome measure will be the change of pulmonary capillary wedge pressure (PCWP) from baseline to 8 hours versus placebo.

Secondary Objective:

Secondary ID(s)

Bay 58-2667/12480