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

October 21, 2014 updated by: Debiopharm International SA

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)

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Drug: Istaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
Drug: Istaroxime
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
Drug: Istaroxime
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours
Experimental: 2
Drug: Istaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
Drug: Istaroxime
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
Drug: Istaroxime
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours
Experimental: 3
Drug: Istaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
Drug: Istaroxime
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PCWP change from baseline
Time Frame: 6 hours after infusion start
6 hours after infusion start

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end.
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
1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Debiopharm International SA

Investigators

  • Study Director: Hein Van Ingen, M.D., Debiopharm International SA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Study Registration Dates

First Submitted

February 5, 2009

First Submitted That Met QC Criteria

February 5, 2009

First Posted (Estimate)

February 6, 2009

Study Record Updates

Last Update Posted (Estimate)

October 23, 2014

Last Update Submitted That Met QC Criteria

October 21, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Debio 0614-202
  • EudraCT number: 2008-003531-21

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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