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

• ClinicalTrials.gov Identifier: NCT03624010
• Recruitment Status: Active, not recruiting
• First Posted: August 9, 2018
• Last Update Posted: April 30, 2021
• Sponsor: Tenax Therapeutics, Inc.
• Information provided by (Responsible Party): Tenax Therapeutics, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hypertension Pulmonary Secondary Heart Failure; Right Sided Heart Failure With Normal Ejection Fraction; Heart Failure With Normal Ejection Fraction	Drug: Levosimendan 2.5 mg/ml Injectable Solution	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Rollover Study of Levosimendan in Patients With Pulmonary Hypertension With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF)
• Actual Study Start Date: November 14, 2018
• Estimated Primary Completion Date: February 2024
• Estimated Study Completion Date: February 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Clinical Safety measured by number of adverse events (AEs ) [ Time Frame: 2 years ]
   Long-term safety profile of levosimendan measured by number of adverse events (AEs )

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford Healthcare

Stanford, California, United States, 94305

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

United States, Minnesota

University of Minnesota Medical Center

Minneapolis, Minnesota, United States, 55455

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Wisconsin

UW Health University Hospital

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Tenax Therapeutics, Inc.

Investigators

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

More Information

• Responsible Party: Tenax Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03624010
• Other Study ID Numbers: TNX-LVO-05
• First Posted: August 9, 2018
• Last Update Posted: April 30, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Heart Failure; Dextrocardia; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Situs Inversus; Lung Diseases; Respiratory Tract Diseases; Simendan; Cardiotonic Agents; Vasodilator Agents; Phosphodiesterase 3 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs