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

NCT00838253 | Withdrawn Phase 2 DMC

• 2 other identifiers: Debio 0614-202EudraCT number: 2008-003531-21
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Heart Failure

Keywords

Acute Heart Failure; Inotropes; Lusitropic agents; Istaroxime; Debio 0614

Outcome Measures

Primary Outcomes (1)

• PCWP change from baseline

  6 hours after infusion start

Secondary Outcomes (2)

• PCWP, MRAP, SVR, PVR, Cardiac Index and SBP

  1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end.

• Safety parameters and drug pharmacokinetics

  1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end

Study Arms (4)

1

EXPERIMENTAL

Drug: Istaroxime

2

EXPERIMENTAL

Drug: Istaroxime

3

EXPERIMENTAL

Drug: Istaroxime

4

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Istaroxime DRUG

Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours

1

Placebo DRUG

Placebo continuous i.v. infusion for 24 hours

4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years;
• Admission for ADHF
• Systolic blood pressure ≤ 120 mmHg;
• Ejection fraction (EF) ≤ 35 %
• Signed informed consent.
• 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

You may not qualify if:

• 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
• Any inotrope administered during the current hospitalization period
• Heart rate \> 120 bpm or \< 50 bpm;

Sponsors & Collaborators

• Debiopharm International SA: lead

Related Publications (1)

• Gheorghiade M, Blair JE, Filippatos GS, Macarie C, Ruzyllo W, Korewicki J, Bubenek-Turconi SI, Ceracchi M, Bianchetti M, Carminati P, Kremastinos D, Valentini G, Sabbah HN; HORIZON-HF Investigators. Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure. J Am Coll Cardiol. 2008 Jun 10;51(23):2276-85. doi: 10.1016/j.jacc.2008.03.015. Epub 2008 Apr 9.

  PMID: 18534276 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

Istaroxime

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Hein Van Ingen, M.D.

  Debiopharm International SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: June 1, 2009
• Last Updated: October 23, 2014

Record last verified: 2014-10