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

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
PCWP change from baseline
Time Frame: 6 hours after infusion start
6 hours after infusion start

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Debiopharm International SA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 6, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 23, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings