Acute Decompensated Heart FailurePhase 2NCT02617446
The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure
A Phase 2 study testing Istaroxime in people with Acute Decompensated Heart Failure, run by Windtree Therapeutics at 11 sites in 2 countries.
Trial summary
To assess the safety, tolerability and efficacy of two different doses of istaroxime, a new agent with lusitropic and inotropic activities that improves the cardiac contraction-relaxation cycle. The 2 doses of istaroxime (0.5 and 1.0 µg/kg/min) will be infused via i. v. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Decompensated 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
- 120 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Dec 2015to 6 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who fulfill the following inclusion criteria at screening will be considered for the study:
- Signed informed consent;
- Male or female patients 18-85 years (inclusive);
- Admission for a recurrent acute decompensated heart failure (ADHF) episode with dyspnea at rest or minimal exertion and need of intravenous diuretic therapy (≥40 mg iv. furosemide);
- Systolic blood pressure between 90 and 125 mmHg (limits included) without signs or symptoms of hypoperfusion including cardiogenic shock, cold extremities and peripheral vasoconstriction, oliguria/anuria, signs of cerebral hypo perfusion such as confusion;
- Left ventricular (LV) Ejection fraction (EF) ≤ 40 % measured by 2D-Echocardiography
Show all 9Show fewer
- E/Ea ratio >10
- BNP ≥ 350pg/mL or NT-pro-BNP ≥1400 pg/mL
- Adequate echocardiography window (defined as visualization of at least 13/16 segment of the left ventricle);
Who cannot join
- Any of the following criteria established at screening would render a patient ineligible for the study:
- Pregnant or breast-feeding women (women of child bearing potential must have the results of a negative pregnancy test recorded prior to study drug administration)
- Current (within 12 hours prior to screening) or planned (through the completion of study drug infusion) treatment with any iv. therapies, including vasodilators (including nitrates or nesiritide), positive inotropic agents and vasopressors
- Current or need of mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device),
- Ongoing treatment with oral digoxin. Patient treated with digoxin within the last week, can be randomised if the plasma concentration of digoxin is tested before randomization and its value will be less than 0.5 ng/ml.
- History of hypersensitivity to the study medication or any related medication
Show all 29Show fewer
- Diagnosis of cardiogenic shock within the past month;
- Acute coronary syndrome or stroke within the past 3 months;
- Coronary artery bypass graft or percutaneous coronary intervention within the past month or planned in the next month;
- Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease;
- Cor pulmonale or other causes of right-sided heart failure (HF) not related to left ventricular dysfunction;
- Pericardial constriction or active pericarditis;
- Atrial fibrillation with marked irregularities of heart rhythm;
- Life threatening ventricular arrhythmia or implantable cardioverter-defibrillator (ICD) shock within the past month;
- Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the past month;
- Valvular disease as primary cause of HF;
- Heart rate >120 bpm or < 50 bpm
- Acute respiratory distress syndrome or ongoing sepsis;
- Fever >38°
- History of bronchial asthma or porphyria;
- Donation or loss of blood equal to or exceeding 500 mL, during the 8 weeks before administration of study medication;
- Positive testing for HIV, Hepatitis B and/or Hepatitis C;
- Participation in another interventional study within the past 30 days;
- The following laboratory exclusion criteria, verified based on results obtained within the last 24 hours of hospitalization:
- Serum creatinine > 3.0 mg/dl (> 265 µmol/L);
- Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 3 x upper limit of normal,
- Hemoglobin (Hb) < 10 g/dL,
- Platelet count < 100,000/µL,
- Serum potassium > 5.3 mmol/L or < 3.8 mmol/L,
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
China9 sites
Fuwai Hospital Chinese Academy of Medical Sciences
Beijing, 100037
Beijing Chao Yang Hospital
Beijing
The 307th Hospital of Chinese People's Liberation Army
Beijing
Lanzhou University No.2 Hospital
Lanzhou, Gansu
The First Hospital of Lanzhou University
Lanzhou, Gansu
Jiangsu Province People's Hospital
Nanjing, Jiangsu
The General Hospital Of Shenyang Military Region
Shenyang, Liaoning
Renmin Hospital of Wuhan University
Wuhan, Hubei
The First Affiliated Hospital Of Xi'an Jiaotong University
Xi'an, Shaanxi
Italy2 sites
University and Civil Hospital of Brescia
Brescia
University of Milano-Bicocca
Milan
About this study
Official title: The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure - A Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel Group Clinical Study
To assess the safety, tolerability and efficacy of two different doses of istaroxime, a new agent with lusitropic and inotropic activities that improves the cardiac contraction-relaxation cycle. The 2 doses of istaroxime (0.5 and 1.0 µg/kg/min) will be infused via i. v. for 24 hours in comparison with placebo, in treatment of Chinese and Italian patients with Acute Decompensated Heart Failure.
Read the detailed description
To assess the safety, tolerability and efficacy of two different doses of istaroxime (0.5 and 1.0 µg/kg/min) in comparison with placebo, including cardiovascular and renal tolerability, as well as changes in biological markers such as N-terminal prohormone brain natriuretic peptide (NT-proBNP) and troponin T (cTnT). The study will be conducted in 96 Chinese and Italian patients with Acute Decompensated Heart Failure. This is a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel group study. Patients were randomly assigned to one of two doses of istaroxime or placebo in a 2:1 ratio within two sequential cohorts of 60 patients each. This 31-day study includes a screening period (Days -1), a treatment period (Day 1), a post-treatment period (Days 2-4), and a follow-up period (which includes one patient visit on Day 30).
In all the Italian patients and in a subset of Chinese patients pharmacokinetics and metabolism of istaroxime shall also be studied.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Placebo, Istaroxime
- Keywords
- safety, efficacy, istaroxime
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
IV of matching saline solution
IstaroximeDrug
IV infusion of 0.5 µg/kg/min or 1.0 µg/kg/min istaroxime
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | IV infusion of placebo for 24 hours Receives: Drug: Placebo |
| Istaroxime 0.5 µg/kg/min | Experimental | The istaroxime treatment dosed at 0.5 µg/kg/min via IV infusion for 24 hours Receives: Drug: Istaroxime |
| Istaroxime 1.0 µg/kg/min | Experimental | The istaroxime treatment dosed at 1.0 µg/kg/min via IV infusion for 24 hours Receives: Drug: Istaroxime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in E/Ea Ratio
Change from baseline at 24 hours in the unitless ratio of E (cm/sec) to Ea (or e') (cm/sec) as measured by echocardiogram.
The endpoint is the Tissue Doppler echocardiography showing measurement of mitral E/Ea ratio for assessment of diastolic dysfunction. Initially mitral E wave is measured. After that, color Tissue Doppler (tissue velocity imaging or TVI) mode is switched on to assess tissue Doppler. The cursor is placed over the medial mitral annulus and tissue Doppler tracing obtained. This allows Ea velocity to be measured. Higher values are suggestive of a worse outcome; less than 8 is normal.
Measured: 24 hours
Secondary outcomes (6)
Change in LVEF
Change from baseline at 24 hours in LV ejection fraction (LVEF) by tissue Doppler
Measured: 24 hours
Change in SVI
Change from baseline at 24 hours in stroke volume index (SVI) by tissue Doppler
Measured: 24 hours
Change in E/A Ratio
Change from baseline at 24 hours in E/A ratio by tissue Doppler
Measured: 24 hours
Change in LV End Systolic Volume
Change from baseline in left ventricular end systolic volume (LVESV) by tissue Doppler
Measured: 24 hours
Change in LV End Diastolic Volume
Change from baseline in left ventricular end diastolic volume (LVEDV) by tissue Doppler
Measured: 24 hours
Change in Dyspnea
Measured using a visual analog scale (0 to 100). Higher scores indicate less dyspnea.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study startDec 2015
- Primary completion14 Aug 2018
- Study completion6 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Decompensated 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
- Intervention model
- Parallel groups
- Model description
- Cohort I: Participants enrolled in a 2:1 ratio to istaroxime 0.5 µg/kg/min or placebo. Cohort II: Participants enrolled in a 2:1 ratio to istaroxime 1.0 µg/kg/min or placebo. Cohort I was enrolled first, followed by Cohort II.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Windtree Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Giuseppe Bianchi, MD, Principal investigator, Windtree Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02617446
- Sponsor's protocol ID
- CVT-CV-002
- Other IDs
- 2013-000540-26, 2015L00219
- Status last verified
- Apr 2023
- First submitted
- 9 Jul 2015
- Last updated
- 24 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Carubelli V, Zhang Y, Metra M, Lombardi C, Felker GM, Filippatos G, O'Connor CM, Teerlink JR, Simmons P, Segal R, Malfatto G, La Rovere MT, Li D, Han X, Yuan Z, Yao Y, Li B, Lau LF, Bianchi G, Zhang J; Istaroxime ADHF Trial Group. Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Eur J Heart Fail. 2020 Sep;22(9):1684-1693. doi: 10.1002/ejhf.1743. Epub 2020 Jan 23.
PubMed 31975496
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure - A Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel Group Clinical Study
- ClinicalTrials.gov ID
- NCT02617446
- Acronym / sponsor ID
- CVT-CV-002
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- safety, efficacy, istaroxime
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Windtree TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- 14 Aug 2018 (actual)
- Study completion
- 6 Feb 2019 (actual)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Posted 24 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety, tolerability and efficacy of two different doses of istaroxime, a new agent with lusitropic and inotropic activities that improves the cardiac contraction-relaxation cycle. The 2 doses of istaroxime (0.5 and 1.0 µg/kg/min) will be infused via i. v. for 24 hours in comparison with placebo, in treatment of Chinese and Italian patients with Acute Decompensated Heart Failure.
Detailed description
To assess the safety, tolerability and efficacy of two different doses of istaroxime (0.5 and 1.0 µg/kg/min) in comparison with placebo, including cardiovascular and renal tolerability, as well as changes in biological markers such as N-terminal prohormone brain natriuretic peptide (NT-proBNP) and troponin T (cTnT). The study will be conducted in 96 Chinese and Italian patients with Acute Decompensated Heart Failure. This is a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel group study. Patients were randomly assigned to one of two doses of istaroxime or placebo in a 2:1 ratio within two sequential cohorts of 60 patients each. This 31-day study includes a screening period (Days -1), a treatment period (Day 1), a post-treatment period (Days 2-4), and a follow-up period (which includes one patient visit on Day 30).
In all the Italian patients and in a subset of Chinese patients pharmacokinetics and metabolism of istaroxime shall also be studied.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Cohort I: Participants enrolled in a 2:1 ratio to istaroxime 0.5 µg/kg/min or placebo. Cohort II: Participants enrolled in a 2:1 ratio to istaroxime 1.0 µg/kg/min or placebo. Cohort I was enrolled first, followed by Cohort II.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIV infusion of placebo for 24 hours |
| Istaroxime 0.5 µg/kg/min | Experimental | Drug: IstaroximeThe istaroxime treatment dosed at 0.5 µg/kg/min via IV infusion for 24 hours |
| Istaroxime 1.0 µg/kg/min | Experimental | Drug: IstaroximeThe istaroxime treatment dosed at 1.0 µg/kg/min via IV infusion for 24 hours |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients who fulfill the following inclusion criteria at screening will be considered for the study:
- Signed informed consent;
- Male or female patients 18-85 years (inclusive);
- Admission for a recurrent acute decompensated heart failure (ADHF) episode with dyspnea at rest or minimal exertion and need of intravenous diuretic therapy (≥40 mg iv. furosemide);
- Systolic blood pressure between 90 and 125 mmHg (limits included) without signs or symptoms of hypoperfusion including cardiogenic shock, cold extremities and peripheral vasoconstriction, oliguria/anuria, signs of cerebral hypo perfusion such as confusion;
Key exclusion criteria (29 listed)
- Any of the following criteria established at screening would render a patient ineligible for the study:
- Pregnant or breast-feeding women (women of child bearing potential must have the results of a negative pregnancy test recorded prior to study drug administration)
- Current (within 12 hours prior to screening) or planned (through the completion of study drug infusion) treatment with any iv. therapies, including vasodilators (including nitrates or nesiritide), positive inotropic agents and vasopressors
- Current or need of mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device),
- Ongoing treatment with oral digoxin. Patient treated with digoxin within the last week, can be randomised if the plasma concentration of digoxin is tested before randomization and its value will be less than 0.5 ng/ml.
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 |
|---|---|---|
| PlaceboIV of matching saline solution | Drug | Placebo |
| IstaroximeIV infusion of 0.5 µg/kg/min or 1.0 µg/kg/min istaroxime | Drug | Istaroxime 0.5 µg/kg/min, Istaroxime 1.0 µg/kg/min |
Primary outcome
Change in E/Ea Ratio
Time frame: 24 hours
Change from baseline at 24 hours in the unitless ratio of E (cm/sec) to Ea (or e') (cm/sec) as measured by echocardiogram. The endpoint is the Tissue Doppler echocardiography showing measurement of mitral E/Ea ratio for assessment of diastolic dysfunction. Initially mitral E wave is measured. After that, color Tissue Doppler (tissue velocity imaging or TVI) mode is switched on to assess tissue Doppler. The cursor is placed over the medial mitral annulus and tissue Doppler tracing obtained. This allows Ea velocity to be measured. Higher values are suggestive of a worse outcome; less than 8 is normal.
6 secondary outcomes
Change in LVEF
Time frame: 24 hours
Change in SVI
Time frame: 24 hours
Change in E/A Ratio
Time frame: 24 hours
Change in LV End Systolic Volume
Time frame: 24 hours
Change in LV End Diastolic Volume
Time frame: 24 hours
Change in Dyspnea
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31975496Carubelli V, Zhang Y, Metra M, Lombardi C, Felker GM, Filippatos G, O'Connor CM, Teerlink JR, Simmons P, Segal R, Malfatto G, La Rovere MT, Li D, Han X, Yuan Z, Yao Y, Li B, Lau LF, Bianchi G, Zhang J; Istaroxime ADHF Trial Group. Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Eur J Heart Fail. 2020 Sep;22(9):1684-1693. doi: 10.1002/ejhf.1743. Epub 2020 Jan 23.
- Individual participant dataSharing planned: No
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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.
Giuseppe Bianchi, MD principal investigator
Windtree Therapeutics, Inc.
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Istaroxime in people with Acute Decompensated Heart Failure, run by Windtree Therapeutics at 11 sites in 2 countries.
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 9 inclusion and 29 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: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in E/Ea Ratio (time frame: 24 hours). 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 NCT02617446, 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 24 May 2023.