Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF (HELP)

Tenax Therapeutics

Status and phase: Completed; Phase 2

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

Treatments: Drug: Matching Placebo; Drug: Levosimendan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03541603

TNX-LVO-04

Details and patient eligibility

About

Phase 2 study to evaluate the efficacy and safety of intermittent levosimendan compared with placebo in hemodynamic improvement with exercise in PH-HFpEF subjects

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups, including a placebo group

Levosimendan 2.5mg/mL Injectable Solution

Experimental group

Description:

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

Treatment:

Drug: Levosimendan

Matching Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Matching Placebo