Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF

NCT ID: NCT03541603

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-14
• Study Completion Date: 2020-04-07

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

Detailed Description

Levosimendan and its prolonged active metabolite, OR-1896, have been shown to have favorable hemodynamic effects in subjects with pulmonary hypertension and right heart failure. Clinical studies that have been conducted in subjects with right heart failure and pulmonary hypertension suggest levosimendan may be an effective therapy in treatment of subjects with PH-HFpEF. This study will provide demonstration of levosimendan/OR-1896's effectiveness in critical measures of hemodynamic response in weekly administration of levosimendan and the concomitant response as measured by exercise capacity, subject quality of life, and changes in functional capacity. These data will support and guide the Phase 3 development of levosimendan in PH-HFpEF subjects.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levosimendan 2.5mg/mL Injectable Solution

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

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: 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

Matching Placebo

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

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: 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

Interventions

Levosimendan

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

Intervention Type: DRUG

Matching Placebo

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

Intervention Type: DRUG

Other Intervention Names

Levosimendan 2.5 mg/mL Injectable Solution; Placebo

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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
• Patients having severely compromised immune function
• Pregnant, suspected to be pregnant, or breast-feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tenax Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford Healthcare

Stanford, California, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

North Shore University Hospital

Manhasset, New York, United States

New York Presbyterian Hospital-Weill Cornell Medicine

New York, New York, United States

Ichan School of Medicine at Mount Sinai

New York, New York, United States

Christ Hospital

Cincinnati, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

UW Health University Hospital

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34716759 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33839076 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TNX-LVO-04

Identifier Type: -

Identifier Source: org_study_id