Open-Label Rollover Study of Levosimendan in PH-HFpEF Patients

Open-Label Rollover Study of Levosimendan in Patients With Pulmonary Hypertension With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF)

PH-HFpEF patients will receive weekly open-label doses of levosimendan and be periodically evaluated for safety and effectiveness in extended use.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure With Normal Ejection Fraction; Hypertension Pulmonary Secondary Heart Failure; Right Sided Heart Failure With Normal Ejection Fraction
• Intervention / Treatment: Drug: Levosimendan 2.5 mg/ml Injectable Solution

Detailed Description

This study will enroll PH-HFpEF patients that have completed a controlled levosimendan study. These patients will receive weekly open-label doses of levosimendan and be periodically evaluated for safety and effectiveness in extended use.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Health University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide a personally signed and dated informed consent document prior to initiation of any study-related procedures that are not considered standard of care.
2. Completed double-blind therapy in a PH-HFpEF clinical study sponsored by Tenax Therapeutics, Inc.
3. May, in the opinion of the Investigator, benefit from continued levosimendan treatment.
4. Female patients of childbearing potential must agree to use a highly effective method of contraception.
5. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Discontinued treatment in the parent study for any reason other than study completion or Sponsor termination of the study.
2. Pregnant or breastfeeding women.
3. Local access to commercially available levosimendan
4. Inability to comply with planned study procedures
5. Patients with scheduled lung or heart transplant or cardiac surgery
6. Dialysis developed since enrollment in parent study (either hemodialysis, peritoneal dialysis, continuous venovenous hemofiltration, or ultrafiltration)
7. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
8. Liver dysfunction with Child Pugh Class B or C (see Attachment 2)
9. Evidence of systemic bacterial, systemic fungal, or viral infection refractory to treatment
10. Weight >150kg
11. Systolic blood pressure (SBP) cannot be managed to ensure SBP >100 mmHg at initiation of study drug
12. Heart rate >100 bpm with study drug, persistent for at least 10 minutes at screening.
13. Hemoglobin < 80 g/L
14. Serum potassium < 3.0 mmol/L or > 5.5 mmol/L at baseline that is unresponsive to management

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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	Drug: Levosimendan 2.5 mg/ml Injectable Solution; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Safety measured by number of adverse events (AEs )	Long-term safety profile of levosimendan measured by number of adverse events (AEs )	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute walk test (6MWT)	Exercise capacity, measured as a distance traveled in 6 minutes	2 years
Patient global assessment	Patient's assessment of well-being, based on a six-point Likert scale (1 =worst, 5= best)	2 years
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)	2 years
Clinical Events: Death and hospitalizations	Incidence of death or hospitalization	2 years

Collaborators and Investigators

• Sponsor: Tenax Therapeutics, Inc.
• Investigators: Principal Investigator: Stuart Rich, MD, Tenax Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 14, 2018
• Primary Completion (ANTICIPATED): February 1, 2024
• Study Completion (ANTICIPATED): February 1, 2024

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (ACTUAL): August 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Situs Inversus; Heart Failure; Hypertension; Hypertension, Pulmonary; Dextrocardia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: TNX-LVO-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No