Safety and Efficacy Study of Istaroxime in Acute Decompensated Heart Failure Patients

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the safety and efficacy of istaroxime in patients hospitalized for Acute Decompensated Heart Failure (ADHF) not requiring inotropic therapy.This will be done by comparing the hemodynamic effect of a 24-hour infusion of three different doses of the drug versus placebo. Efficacy will be measured as a change in Pulmonary Capillary Wedge Pressure from pre-infusion to 6 hours after infusion start. Secondary objectives will include the evaluation of clinical efficacy and safety through assessment of cardiovascular and renal tolerability as well as changes in biological markers such as brain natriuretic peptide (BNP) and troponin I (TNI), and the neurohormones renin and aldosterone and also to assess the pharmacokinetics of istaroxime and its metabolites.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Debiopharm International SA

Criteria

Inclusion Criteria:

• Male or female patients ≥18 years;

• Admission for ADHF

• Systolic blood pressure ≤ 120 mmHg;

• Ejection fraction (EF) ≤ 35 %

• Signed informed consent.

Randomization inclusion criteria:

• Persistence of ADHF signs despite initial treatment with i.v. diuretics and/or vasodilators;

• Cardiac index ≤ 2.5 L/min/m²;

• Pulmonary capillary wedge pressure ≥ 20 mmHg

• Systolic BP between 85 and 120 mmHg (limits included) without signs or symptoms of hypoperfusion

Exclusion Criteria:

• Main screening exclusion criteria:

• Positive pregnancy test in females of childbearing potential;

• Systolic blood pressure < 85 mmHg or > 120 mmHg;

• Oral treatment with digoxin within one week before current hospitalization;

• Any inotrope administered during the current hospitalization

• Presence of cardiogenic shock or its occurrence within the past month;

• Acute coronary syndrome within the past 3 months;

• Coronary artery bypass graft or percutaneous coronary intervention within the past month;

• Stroke within the past 6 months;

• Atrial fibrillation with uncontrolled HR (HR > 100 beats per minute (bpm);

• Life threatening ventricular arrhythmia or ICD (implantable cardioverter defibrillator) shock within the past month;

• Presence of a CRT (cardiac resynchronization therapy), ICD or pacemaker devices implanted within the past month;

• Second or third degree atrio-ventricular block without pacemaker;

• Abnormal safety lab values obtained within the last 24 hours of the screening period prior to pulmonary arterial catheter (PAC) insertion

Randomization exclusion criteria:

• Any inotrope administered during the current hospitalization period

• Heart rate > 120 bpm or < 50 bpm;

• cTnI > 0.5 ng/mL or cTnI > ULN and > 1.25x the first screening assessment