Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF

Heart Failure With Normal Ejection Fraction Clinical Trial

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Official title:

A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PH-HFpEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03541603
• Other study ID #: TNX-LVO-04
• Status: Completed
• Phase: Phase 2
• Start date: November 14, 2018
• Est. completion date: April 7, 2020

Study information

• Verified date: April 2020
• Source: Tenax Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: April 7, 2020
• Est. primary completion date: April 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	UW Health University Hospital	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Ichan School of Medicine at Mount Sinai	New York	New York
United States	New York Presbyterian Hospital-Weill Cornell Medicine	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford Healthcare	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Tenax Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Cardiac Index (CI) at Rest and With Exercise.	Change in Cardiac Index (CI) at rest and with exercise at Week 6 (CI determined by thermodilution) (CI is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA))	Baseline, Week 6
Secondary	Change in Pulmonary Vascular Resistance (PVR) Effect at Rest and With Exercise	Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise at Week 6	Baseline, Week 6
Secondary	Change in PCWP When Supine and Legs Elevated	Change in Pulmonary Capillary Wedge Pressure, Baseline to Week 6	Baseline, Week 6
Secondary	Patient Global Assessment	Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best) (minimum total score 5pts, maximum total score 25 pts) (no comparison to baseline as no instrument used at baseline)	Baseline, Week 6
Secondary	Exercise Duration Via 6 Minute Walk Test	Change in 6-minute walk test at Week 6 vs baseline	Baseline, Week 6
Secondary	Physician's Assessment of Functional Class	Physician's Assessment of New York Heart Association (NYHA) Classification (one of four categories based on how much the patient is limited during physical activity. (Class I, no limitation of physical activity to Class IV, marked limitation of physical activity).	Baseline, Week 6
Secondary	Number of Participants With Composite Events of Death or Hospitalization	Number of Participants with Composite Events of death or hospitalization through Week 6	Baseline, Week 6