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

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

Detailed Description
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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.

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

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

Intervention / Treatment
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* Drug: Levosimendan 2.5 mg/ml Injectable Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide a personally signed and dated informed consent document prior to initiation of any study-related procedures that are not considered standard of care. Completed double-blind therapy in a PH-HFpEF clinical study sponsored by Tenax Therapeutics, Inc. May, in the opinion of the Investigator, benefit from continued levosimendan treatment. Female patients of childbearing potential must agree to use a highly effective method of contraception. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria: Discontinued treatment in the parent study for any reason other than study completion or Sponsor termination of the study. Pregnant or breastfeeding women. Local access to commercially available levosimendan Inability to comply with planned study procedures Patients with scheduled lung or heart transplant or cardiac surgery Dialysis developed since enrollment in parent study (either hemodialysis, peritoneal dialysis, continuous venovenous hemofiltration, or ultrafiltration) Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 Liver dysfunction with Child Pugh Class B or C (see Attachment 2) Evidence of systemic bacterial, systemic fungal, or viral infection refractory to treatment Weight >150kg Systolic blood pressure (SBP) cannot be managed to ensure SBP >100 mmHg at initiation of study drug Heart rate >100 bpm with study drug, persistent for at least 10 minutes at screening. Hemoglobin < 80 g/L Serum potassium < 3.0 mmol/L or > 5.5 mmol/L at baseline that is unresponsive to management

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levosimendan<br>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<br>* 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<br>|

What is the study measuring?
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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 |