Heart FailurePhase 2NCT00838253
Safety and Efficacy Study of Istaroxime in Acute Decompensated Heart Failure Patients
A Phase 2 study testing Istaroxime in people with Heart Failure, run by Debiopharm International SA.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Istaroxime
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥18 years;
- Admission for ADHF
- Systolic blood pressure ≤ 120 mmHg;
- Ejection fraction (EF) ≤ 35 %
- Signed informed consent.
- Randomization inclusion criteria:
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- 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
Who cannot join
- 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;
Show all 18Show fewer
- 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
About this study
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)
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Istaroxime, Placebo
- Keywords
- Acute Heart Failure, Inotropes, Lusitropic agents, Istaroxime, Debio 0614
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IstaroximeDrug
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
IstaroximeDrug
Istaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours
IstaroximeDrug
Istaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours
PlaceboDrug
Placebo continuous i.v. infusion for 24 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Istaroxime |
| 2 | Experimental | Not described Receives: Drug: Istaroxime |
| 3 | Experimental | Not described Receives: Drug: Istaroxime |
| 4 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PCWP change from baseline
Measured: 6 hours after infusion start
Secondary outcomes (2)
PCWP, MRAP, SVR, PVR, Cardiac Index and SBP
Measured: 1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end.
Safety parameters and drug pharmacokinetics
Measured: 1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2009 (estimated)
- Study startJun 2009
Why it stopped: The study was not started due to a re-evaluation of the istaroxime development program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Debiopharm International SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Hein Van Ingen, M.D., Study director, Debiopharm International SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00838253
- Sponsor's protocol ID
- Debio 0614-202
- Other IDs
- EudraCT number: 2008-003531-21
- Status last verified
- Oct 2014
- First submitted
- 5 Feb 2009
- Last updated
- 23 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18534276
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00838253
- Acronym / sponsor ID
- Debio 0614-202
- Conditions
- Heart Failure
- Keywords
- Acute Heart Failure, Inotropes, Lusitropic agents, Istaroxime, Debio 0614
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was not started due to a re-evaluation of the istaroxime development program
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Debiopharm International SAIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- First posted
- 6 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Istaroxime |
| 2 | Experimental | Drug: Istaroxime |
| 3 | Experimental | Drug: Istaroxime |
| 4 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients ≥18 years;
- Admission for ADHF
- Systolic blood pressure ≤ 120 mmHg;
- Ejection fraction (EF) ≤ 35 %
- Signed informed consent.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IstaroximeIstaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 1 |
| IstaroximeIstaroxime 1.0 μg/kg/min (60 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 2 |
| IstaroximeIstaroxime 1.5 μg/kg/min (90 μg/kg/h) continuous i.v. infusion for 24 hours | Drug | 3 |
| PlaceboPlacebo continuous i.v. infusion for 24 hours | Drug | 4 |
Primary outcome
PCWP change from baseline
Time frame: 6 hours after infusion start
2 secondary outcomes
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.
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2014.
- Background: PubMed 18534276Gheorghiade 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hein Van Ingen, M.D. study director
Debiopharm International SA
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Istaroxime in people with Heart Failure, run by Debiopharm International SA.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PCWP change from baseline (time frame: 6 hours after infusion start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00838253, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2014.