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Withdrawn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
Istaroxime
Istaroxime
Placebo
Sponsored by
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
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
Experimental
Experimental
Placebo Comparator
Arm Label
1
2
3
4
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
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Arm Title
3
Arm Type
Experimental
Arm Title
4
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
No
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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