Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF

NCT03541603 | Completed Phase 2 Results FDA Drug

• 1 other identifier: TNX-LVO-04
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 16

Brief Summary

Phase 2 study to evaluate the efficacy and safety of intermittent levosimendan compared with placebo in hemodynamic improvement with exercise in PH-HFpEF subjects

Conditions

Hypertension Pulmonary Secondary; Heart Failure, Right Sided; Heart Failure With Normal Ejection Fraction

Keywords

PH-HFpEF

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Pulmonary Capillary Wedge Pressure (PCWP) With Bicycle Exercise

  Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise at Week 6

  Baseline, Week 6

Secondary Outcomes (7)

• Change in Cardiac Index (CI) at Rest and With Exercise.

  Baseline, Week 6

• Change in Pulmonary Vascular Resistance (PVR) Effect at Rest and With Exercise

  Baseline, Week 6

• Change in PCWP When Supine and Legs Elevated

  Baseline, Week 6

• Patient Global Assessment

  Baseline, Week 6

• Exercise Duration Via 6 Minute Walk Test

  Baseline, Week 6

Study Arms (2)

Levosimendan 2.5mg/mL Injectable Solution

EXPERIMENTAL

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Drug: Levosimendan

Matching Placebo

PLACEBO COMPARATOR

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Drug: Matching Placebo

Interventions

Levosimendan DRUG

A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Also known as: Levosimendan 2.5 mg/mL Injectable Solution

Levosimendan 2.5mg/mL Injectable Solution

Matching Placebo DRUG

A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Also known as: Placebo

Matching Placebo

Eligibility Criteria

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

You may qualify if:

• Criteria to enter Open-label, Lead-in Dose Phase:
• Diagnosis of World Health Organization (WHO) Group 2 Pulmonary Hypertension (PH) with Heart Failure with Preserved Ejection Fraction (HFpEF) confirmed at the time of the diagnosis of pulmonary hypertension.
• Baseline Pulmonary Arterial Pressure (PAP) ≥35, Pulmonary Capillary Wedge Pressure (PCWP) ≥20, New York Heart Association (NYHA) Class IIb/III, Left Ventricular Ejection Fraction (LVEF) ≥40%
• Ability to walk at least 50 meters, but not more than 550 meters in a six-minute walk test.
• Stable oxygen treatment (if applicable), and medications for heart failure, hypertension, and respiratory condition
• Criterion for Randomization to Double-blind Phase:
• Response to Open-label, Lead-in Levosimendan: Patients who demonstrate a ≥4mmHg reduction in PCWP from baseline measured at bicycle exercise (25 watts) with no more than a 10% decrease from baseline in cardiac index

You may not qualify if:

• Subject has a primary diagnosis of PH other than Group 2 PH-HFpEF
• Previous Percutaneous Coronary Intervention (PCI) or cardiac surgery (CABG), unless they have a negative stress test in the last 12 months)
• Congenital heart disease
• Clinically significant lung disease
• Planned heart or lung surgery
• Cardiac Index \>4.0 L/min/m2
• Concomitant administration of pulmonary vasodilator therapy or taken within 14 days
• Dialysis or Glomerular Filtration Rate (GFR) \<30 mL/min/1.73 m2
• Liver dysfunction with Child-Pugh Class B or C
• Evidence of systemic infection
• Weight \> 150kg
• Symptomatic systolic blood pressure (SBP) cannot be managed to ensure SBP \>100 mmHg
• Heart rate \>= 100 bpm with the study drug, symptomatic and persistent for at least 10 minutes
• Hemoglobin \< 80 g/L
• Serum potassium \< 3.0 mmol/L or \> 5.5 mmol/L at baseline

Sponsors & Collaborators

• Tenax Therapeutics, Inc.: lead

Study Sites (16)

Stanford Healthcare

Stanford, California, 94305, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

New York Presbyterian Hospital-Weill Cornell Medicine

New York, New York, 10021, United States

Location

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UW Health University Hospital

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• Burkhoff D, Rich S, Pollesello P, Papp Z. Levosimendan-induced venodilation is mediated by opening of potassium channels. ESC Heart Fail. 2021 Dec;8(6):4454-4464. doi: 10.1002/ehf2.13669. Epub 2021 Oct 30.

  PMID: 34716759 DERIVED

• Burkhoff D, Borlaug BA, Shah SJ, Zolty R, Tedford RJ, Thenappan T, Zamanian RT, Mazurek JA, Rich JD, Simon MA, Chung ES, Raza F, Majure DT, Lewis GD, Preston IR, Rich S. Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial. JACC Heart Fail. 2021 May;9(5):360-370. doi: 10.1016/j.jchf.2021.01.015. Epub 2021 Apr 7.

  PMID: 33839076 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Simendan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Hemodynamic effects at Wk6 were measured \~1 week after final levosimendan infusion. Thus, hemodynamic effects at 6 weeks represent effects at trough levels; greater effects might have been observed with earlier assessment. No previous study evaluated chronic levosimendan in PH-HFpEF. Chose a low dose out of an abundance of caution. It remains possible that higher doses may be more effective in selected patients.

Results Point of Contact

• Title: Stuart Rich, MD; Chief Medical Officer
• Organization: Tenax Therapeutics, Inc.

s.rich@tenaxthera.com

919 855 2100

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 30, 2018
• Study Start: November 14, 2018
• Primary Completion: April 7, 2020
• Study Completion: April 7, 2020
• Last Updated: November 20, 2024
• Results First Posted: May 14, 2024

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)