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

November 18, 2024 updated by: Tenax Therapeutics, Inc.

A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PH-HFpEF)

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford Healthcare
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New York
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10029
        • Ichan School of Medicine at Mount Sinai
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital-Weill Cornell Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Christ Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Presbyterian Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • UW Health University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline Pulmonary Capillary Wedge Pressure (PCWP) With Bicycle Exercise
Time Frame: Baseline, Week 6
Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise at Week 6
Baseline, Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Cardiac Index (CI) at Rest and With Exercise.
Time Frame: Baseline, Week 6
Change in Cardiac Index (CI) at rest and with exercise at Week 6 (CI determined by thermodilution) (CI is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA))
Baseline, Week 6
Change in Pulmonary Vascular Resistance (PVR) Effect at Rest and With Exercise
Time Frame: Baseline, Week 6
Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise at Week 6
Baseline, Week 6
Change in PCWP When Supine and Legs Elevated
Time Frame: Baseline, Week 6
Change in Pulmonary Capillary Wedge Pressure, Baseline to Week 6
Baseline, Week 6
Patient Global Assessment
Time Frame: Baseline, Week 6
Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best) (minimum total score 5pts, maximum total score 25 pts) (no comparison to baseline as no instrument used at baseline)
Baseline, Week 6
Exercise Duration Via 6 Minute Walk Test
Time Frame: Baseline, Week 6
Change in 6-minute walk test at Week 6 vs baseline
Baseline, Week 6
Physician's Assessment of Functional Class
Time Frame: Baseline, 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).
Baseline, Week 6
Number of Participants With Composite Events of Death or Hospitalization
Time Frame: Baseline, Week 6
Number of Participants with Composite Events of death or hospitalization through Week 6
Baseline, Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tenax Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 14, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 7, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 7, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TNX-LVO-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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