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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. Identifier: NCT03541603
Recruitment Status : Completed
First Posted : May 30, 2018
Last Update Posted : April 10, 2020
Information provided by (Responsible Party):
Tenax Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE May 3, 2018
First Posted Date  ICMJE May 30, 2018
Last Update Posted Date April 10, 2020
Actual Study Start Date  ICMJE November 14, 2018
Actual Primary Completion Date April 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise [ Time Frame: Week 6 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
  • Change in Cardiac Index (CI) at rest and with exercise [ Time Frame: Week 6 ]
  • Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise [ Time Frame: Week 6 ]
  • Change in PCWP when supine and legs elevated [ Time Frame: Week 6 ]
  • 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)
  • Exercise duration via 6 minute walk test [ Time Frame: Week 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).
  • Composite incidence of death or hospitalization [ Time Frame: Week 6 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF
Official Title  ICMJE A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF)
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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertension Pulmonary Secondary
  • Heart Failure, Right Sided
  • Heart Failure With Normal Ejection Fraction
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Levosimendan 2.5mg/mL Injectable Solution
    0.075 - 0.1µg/kg/min for 24 hrs (weekly)
    Intervention: Drug: Levosimendan
  • Placebo Comparator: Matching Placebo
    0.075 - 0.1µg/kg/min for 24 hrs (weekly)
    Intervention: Drug: Matching Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2018)
Actual Study Completion Date  ICMJE April 7, 2020
Actual Primary Completion Date April 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03541603
Other Study ID Numbers  ICMJE TNX-LVO-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tenax Therapeutics, Inc.
Study Sponsor  ICMJE Tenax Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Tenax Therapeutics, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP