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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Levosimendan
Matching Placebo
Sponsored by
Tenax Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension Pulmonary Secondary focused on measuring PH-HFpEF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford Healthcare
  • Northwestern Memorial Hospital
  • Tufts Medical Center
  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • University of Minnesota Medical Center
  • Mayo Clinic
  • University of Nebraska Medical Center
  • North Shore University Hospital
  • New York Presbyterian Hospital-Weill Cornell Medicine
  • Ichan School of Medicine at Mount Sinai
  • Christ Hospital
  • Hospital of the University of Pennsylvania
  • University of Pittsburgh Presbyterian Hospital
  • Medical University of South Carolina
  • UW Health University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Levosimendan 2.5mg/mL Injectable Solution

Matching Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise

Secondary Outcome Measures

Change in Cardiac Index (CI) at rest and with exercise
Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise
Change in PCWP when supine and legs elevated
Patient global assessment
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
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).
Composite incidence of death or hospitalization

Full Information

First Posted
May 3, 2018
Last Updated
April 9, 2020
Sponsor
Tenax Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03541603
Brief Title
Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF
Acronym
HELP
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
November 14, 2018 (Actual)
Primary Completion Date
April 7, 2020 (Actual)
Study Completion Date
April 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tenax Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension Pulmonary Secondary, Heart Failure, Right Sided, Heart Failure With Normal Ejection Fraction
Keywords
PH-HFpEF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levosimendan 2.5mg/mL Injectable Solution
Arm Type
Experimental
Arm Description
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Description
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Intervention Type
Drug
Intervention Name(s)
Levosimendan
Other Intervention Name(s)
Levosimendan 2.5 mg/mL Injectable Solution
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Other Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Change in Cardiac Index (CI) at rest and with exercise
Time Frame
Week 6
Title
Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise
Time Frame
Week 6
Title
Change in PCWP when supine and legs elevated
Time Frame
Week 6
Title
Patient global assessment
Description
Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best)
Time Frame
Week 6
Title
Exercise duration via 6 minute walk test
Time Frame
Week 6
Title
Physician's assessment of functional class
Description
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).
Time Frame
Week 6
Title
Composite incidence of death or hospitalization
Time Frame
Week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Stanford Healthcare
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
New York Presbyterian Hospital-Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Ichan School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Presbyterian Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
UW Health University Hospital
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34716759
Citation
Burkhoff D, Rich S, Pollesello P, Papp Z. Levosimendan-induced venodilation is mediated by opening of potassium channels. ESC Heart Fail. 2021 Dec;8(6):4454-4464. doi: 10.1002/ehf2.13669. Epub 2021 Oct 30.
Results Reference
derived
PubMed Identifier
33839076
Citation
Burkhoff D, Borlaug BA, Shah SJ, Zolty R, Tedford RJ, Thenappan T, Zamanian RT, Mazurek JA, Rich JD, Simon MA, Chung ES, Raza F, Majure DT, Lewis GD, Preston IR, Rich S. Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial. JACC Heart Fail. 2021 May;9(5):360-370. doi: 10.1016/j.jchf.2021.01.015. Epub 2021 Apr 7.
Results Reference
derived

Learn more about this trial

Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF

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