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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03541603
Recruitment Status : Completed
First Posted : May 30, 2018
Last Update Posted : April 10, 2020
Information provided by (Responsible Party):
Tenax Therapeutics, Inc.

Brief 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

Condition or disease Intervention/treatment Phase
Hypertension Pulmonary Secondary Heart Failure, Right Sided Heart Failure With Normal Ejection Fraction Drug: Levosimendan Drug: Matching Placebo Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF)
Actual Study Start Date : November 14, 2018
Actual Primary Completion Date : April 7, 2020
Actual Study Completion Date : April 7, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Levosimendan 2.5mg/mL Injectable Solution
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
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
Other Name: Levosimendan 2.5 mg/mL Injectable Solution

Placebo Comparator: Matching Placebo
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Drug: 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
Other Name: Placebo

Primary Outcome Measures :
  1. Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise [ Time Frame: Week 6 ]

Secondary Outcome Measures :
  1. Change in Cardiac Index (CI) at rest and with exercise [ Time Frame: Week 6 ]
  2. Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise [ Time Frame: Week 6 ]
  3. Change in PCWP when supine and legs elevated [ Time Frame: Week 6 ]
  4. Patient global assessment [ Time Frame: Week 6 ]
    Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best)

  5. Exercise duration via 6 minute walk test [ Time Frame: Week 6 ]
  6. Physician's assessment of functional class [ Time Frame: Week 6 ]
    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).

  7. Composite incidence of death or hospitalization [ Time Frame: Week 6 ]

Information from the National Library of Medicine

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

Inclusion Criteria:

Criteria to enter Open-label, Lead-in Dose Phase:

  • Diagnosis of WHO Group 2 Pulmonary Hypertension (PH) with heart failure and preserved ejection fraction (HFpEF) confirmed at the time of the diagnosis of pulmonary hypertension.
  • Baseline Pulmonary Arterial Pressure (PAP) ≥35, PCWP ≥20, 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 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 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03541603

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United States, California
Stanford Healthcare
Stanford, California, United States, 94305
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
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, New York
North Shore University Hospital
Manhasset, New York, United States, 11030
New York Presbyterian Hospital-Weill Cornell Medicine
New York, New York, United States, 10021
Ichan School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Ohio
Christ Hospital
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh 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.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Tenax Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03541603    
Other Study ID Numbers: TNX-LVO-04
First Posted: May 30, 2018    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tenax Therapeutics, Inc.:
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Heart Failure
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Cardiotonic Agents
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs