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

This study has been withdrawn prior to enrollment.
(The study was not started due to a re-evaluation of the istaroxime development program)
Sponsor:
Information provided by:
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT00838253
First received: February 5, 2009
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Drug: Istaroxime
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • PCWP change from baseline [ Time Frame: 6 hours after infusion start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2009
Arms Assigned Interventions
Experimental: 1 Drug: Istaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
Experimental: 2 Drug: Istaroxime
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
Experimental: 3 Drug: Istaroxime
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours
Placebo Comparator: 4 Drug: Placebo
Placebo continuous i.v. infusion for 24 hours

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838253

Sponsors and Collaborators
Debiopharm International SA
Investigators
Study Director: Hein Van Ingen, M.D. Debiopharm International SA
  More Information

Additional Information:
Publications:
Responsible Party: Dr Hein Van Ingen, M.D., Debiopharm S.A.
ClinicalTrials.gov Identifier: NCT00838253     History of Changes
Other Study ID Numbers: Debio 0614-202, EudraCT number: 2008-003531-21
Study First Received: February 5, 2009
Last Updated: October 21, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation

Keywords provided by Debiopharm International SA:
Acute Heart Failure
Inotropes
Lusitropic agents
Istaroxime
Debio 0614

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on November 20, 2014