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

Primary Purpose

Heart Failure

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Istaroxime

Placebo

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Acute Heart Failure, Inotropes, Lusitropic agents, Istaroxime, Debio 0614

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

PCWP change from baseline

Secondary Outcome Measures

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

Safety parameters and drug pharmacokinetics

Full Information

NCT ID

NCT00838253

First Posted

February 5, 2009

Last Updated

October 21, 2014

Sponsor

Debiopharm International SA

1. Study Identification

Unique Protocol Identification Number

NCT00838253

Brief Title

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

Official Title

A Multicenter, Randomized, Double-blind, Placebo-controlled Staggered Dose-escalating Phase IIb Study of the Safety and Efficacy of Istaroxime Over 24 Hours at Three Doses in Acute Decompensated Heart Failure Patients (The IGNITE Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Withdrawn

Why Stopped

The study was not started due to a re-evaluation of the istaroxime development program

Study Start Date

June 2009 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Debiopharm International SA

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The 32-day study includes a 48-hour screening period, a 30-minute to 2-hour pre treatment period, a maximum 2-hour period for randomization and measurement of baseline values, a 24-hour treatment period, and a 96-hour post-treatment period. A 25-day follow-up period including a visit on Day 30 will take place after the active phase of the study When considered to be eligible, a first cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 0.5 μg/kg/min or placebo. If after the continuous safety monitoring and interim analyses the DMC determines that there are no safety issues with this dose, a second cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 1.0 μg/kg/min or placebo. If after the continuous safety monitoring and interim analyses of the second cohort the DMC determines that there are no safety issues with this dose, a third cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 1.5 μg/kg/min or placebo. In all cohorts, patients will receive standard of care therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Istaroxime

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Istaroxime

Intervention Description

Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours

Intervention Type

Drug

Intervention Name(s)

Istaroxime

Intervention Description

Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo continuous i.v. infusion for 24 hours

Primary Outcome Measure Information:

Title

PCWP change from baseline

Time Frame

6 hours after infusion start

Secondary Outcome Measure Information:

Title

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

Time Frame

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

Title

Safety parameters and drug pharmacokinetics

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hein Van Ingen, M.D.

Organizational Affiliation

Debiopharm International SA

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

18534276

Citation

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.

Results Reference

background

Links:

URL

http://www.debiopharm.com

Description

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

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