The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure

NCT02617446 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CVT-CV-0022013-000540-262015L00219
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 11

Brief 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. for 24 hours in comparison with placebo, in treatment of Chinese and Italian patients with Acute Decompensated Heart Failure.

Conditions

Acute Decompensated Heart Failure

Keywords

safety; efficacy; istaroxime

Outcome Measures

Primary Outcomes (1)

• 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.

  24 hours

Secondary Outcomes (6)

• Change in LVEF

  24 hours

• Change in SVI

  24 hours

• Change in E/A Ratio

  24 hours

• Change in LV End Systolic Volume

  24 hours

• Change in LV End Diastolic Volume

  24 hours

Other Outcomes (19)

• Change in cTnT

  24 hours

• Change in eGFR

  24 Hours

• Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias

  24 hours

Study Arms (3)

Placebo

PLACEBO COMPARATOR

IV infusion of placebo for 24 hours

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

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

Drug: Istaroxime

Interventions

Placebo DRUG

IV of matching saline solution

Placebo

Istaroxime DRUG

IV infusion of 0.5 µg/kg/min or 1.0 µg/kg/min istaroxime

Istaroxime 0.5 µg/kg/min; Istaroxime 1.0 µg/kg/min

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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);

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• Windtree Therapeutics: lead

Study Sites (11)

Lanzhou University No.2 Hospital

Lanzhou, Gansu, China

Location

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Location

Jiangsu Province People's Hospital

Nanjing, Jiangsu, China

Location

The General Hospital Of Shenyang Military Region

Shenyang, Liaoning, China

Location

The First Affiliated Hospital Of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Location

Fuwai Hospital Chinese Academy of Medical Sciences

Beijing, 100037, China

Location

Beijing Chao Yang Hospital

Beijing, China

Location

The 307th Hospital of Chinese People's Liberation Army

Beijing, China

Location

University and Civil Hospital of Brescia

Brescia, Italy

Location

University of Milano-Bicocca

Milan, Italy

Location

Related Publications (1)

• 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.

  PMID: 31975496 RESULT

MeSH Terms

Interventions

Istaroxime

Limitations and Caveats

The major limitation of this study regards enrollment discrepancies between the study populations and sites of the two cohorts, with Cohort 2 enrolling exclusively Asian patients. We observed that patients enrolled in this trial were younger and with a better renal function compared to other studies.

Results Point of Contact

• Title: Phillip D. Simmons, Executive Director of Biostatistics & Data Management
• Organization: Windtree Therapeutics, Inc.

psimmons@windtreetx.com

215-488-9300

Study Officials

• Giuseppe Bianchi, MD

  Windtree Therapeutics, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: December 1, 2015
• Study Start: December 1, 2015
• Primary Completion: August 14, 2018
• Study Completion: February 6, 2019
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); CN (9)