LEVEL-2: LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF-2 (LEVEL-2)

March 12, 2026 updated by: Tenax Therapeutics, Inc.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction

The purpose of this study is to assess the efficacy and safety of the study drug, levosimendan (given orally), compared to placebo in participants with pulmonary hypertension with heart failure with preserved left ventricular ejection fraction (PH-HFpEF) as measured by the change in 6-Minute Walk Distance.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Approximately 540 participants will be randomized in a 2:1 ratio to receive an oral dose of levosimendan or placebo. Participants will be eligible for an open label extension (OLE) of 52-weeks.

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Argentina
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, 1280
        • Not yet recruiting
        • Tenax Investigational Site
    • Corrientes Province
      • Corrientes, Corrientes Province, Argentina, W3400AMZ
        • Not yet recruiting
        • Tenax Investigational Site
    • San Luis Province
      • San Luis, San Luis Province, Argentina, D5702JRS
        • Not yet recruiting
        • Tenax Investigational Site
  • Austria
      • Braunau am Inn, Austria, 5280
        • Not yet recruiting
        • Tenax Investigational Site
      • Graz, Austria, 8036
        • Not yet recruiting
        • Tenax Investigational Site
      • Klagenfurt, Austria, 9020
        • Not yet recruiting
        • Tenax Investigational Site
      • Sankt Pölten, Austria, 3100
        • Not yet recruiting
        • Tenax Investigational Site
      • Vienna, Austria, 1100
        • Not yet recruiting
        • Tenax Investigational Site
  • Brazil
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 40170-130
        • Not yet recruiting
        • Tenax Investigational Site
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30220
        • Not yet recruiting
        • Tenax Investigational Site
    • Paraná
      • Curitiba, Paraná, Brazil, 80215-901
        • Not yet recruiting
        • Tenax Investigational Site
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14026-020
        • Not yet recruiting
        • Tenax Investigational Site
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Not yet recruiting
        • Tenax Investigational Site
      • Sofia, Bulgaria, 1407
        • Not yet recruiting
        • Tenax Investigational Site
      • Sofia, Bulgaria, 1431
        • Not yet recruiting
        • Tenax Investigational Site
      • Sofia, Bulgaria, 1750
        • Not yet recruiting
        • Tenax Investigational Site
  • Czechia
      • Ostrava, Czechia, 72880
        • Not yet recruiting
        • Tenax Investigational Site
      • Prague, Czechia, 10034
        • Not yet recruiting
        • Tenax Investigational Site
      • Prague, Czechia, 15006
        • Not yet recruiting
        • Tenax Investigational Site
  • France
      • Le Kremlin-Bicêtre, France, 94270
        • Not yet recruiting
        • Tenax Investigational Site
      • Montpellier, France, 34295
        • Not yet recruiting
        • Tenax Investigational Site
      • Nantes, France, 44007
        • Not yet recruiting
        • Tenax Investigational Site
      • Nice, France, 06001
        • Not yet recruiting
        • Tenax Investigational Site
      • Pau, France, 64000
        • Not yet recruiting
        • Tenax Investigational Site
  • Germany
      • Bad Bevensen, Germany, 29549
        • Not yet recruiting
        • Tenax Investigational Site
      • Bad Nauheim, Germany, 61231
        • Not yet recruiting
        • Tenax Investigational Site
      • Berlin, Germany, 12683
        • Not yet recruiting
        • Tenax Investigational Site
      • Dresden, Germany, 01307
        • Not yet recruiting
        • Tenax Investigational Site
      • Hamburg, Germany, 20251
        • Not yet recruiting
        • Tenax Investigational Site
      • Jena, Germany, 07747
        • Not yet recruiting
        • Tenax Investigational Site
  • Hungary
      • Budapest, Hungary, 1122
        • Not yet recruiting
        • Tenax Investigational Site
      • Budapest, Hungary, 1134
        • Not yet recruiting
        • Tenax Investigational Site
      • Debrecen, Hungary, 4032
        • Not yet recruiting
        • Tenax Investigational Site
      • Szeged, Hungary, 6275
        • Not yet recruiting
        • Tenax Investigational Site
  • Italy
      • Acquaviva delle Fonti, Italy, 70021
        • Not yet recruiting
        • Tenax Investigational Site
      • Messina, Italy, 98125
        • Not yet recruiting
        • Tenax Investigational Site
      • Milan, Italy, 20132
        • Not yet recruiting
        • Tenax Investigational Site
      • Milan, Italy, 20138
        • Not yet recruiting
        • Tenax Investigational Site
      • Milan, Italy, 20149
        • Not yet recruiting
        • Tenax Investigational Site
      • Pavia, Italy, 27100
        • Not yet recruiting
        • Tenax Investigational Site
      • Pisa, Italy, 56126
        • Not yet recruiting
        • Tenax Investigational Site
      • Roma, Italy, 00168
        • Not yet recruiting
        • Tenax Investigational Site
      • Rozzano, Italy, 20089
        • Not yet recruiting
        • Tenax Investigational Site
  • Poland
      • Poznan, Poland, 61848
        • Not yet recruiting
        • Tenax Investigational Site
      • Wroclaw, Poland, 50556
        • Not yet recruiting
        • Tenax Investigational Site
      • Wroclaw, Poland, 50891
        • Not yet recruiting
        • Tenax Investigational Site
  • South Korea
      • Cheongju-si, South Korea, 28644
        • Not yet recruiting
        • Tenax Investigational Site
      • Gwangju, South Korea, 61469
        • Not yet recruiting
        • Tenax Investigational Site
      • Incheon, South Korea, 21565
        • Not yet recruiting
        • Tenax Investigational Site
      • Seoul, South Korea, 03080
        • Not yet recruiting
        • Tenax Investigational Site
      • Seoul, South Korea, 08308
        • Not yet recruiting
        • Tenax Investigational Site
      • Wŏnju, South Korea, 26426
        • Not yet recruiting
        • Tenax Investigational Site
  • Spain
      • Barcelona, Spain, 08003
        • Not yet recruiting
        • Tenax Investigational Site
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Tenax Investigational Site
      • Barcelona, Spain, 08036
        • Not yet recruiting
        • Tenax Investigational Site
      • Lugo, Spain, 27003
        • Not yet recruiting
        • Tenax Investigational Site
      • Madrid, Spain, 28041
        • Not yet recruiting
        • Tenax Investigational Site
      • Madrid, Spain, 28046
        • Not yet recruiting
        • Tenax Investigational Site
      • Madrid, Spain, 28055
        • Not yet recruiting
        • Tenax Investigational Site
      • Marbella, Spain, 29603
        • Not yet recruiting
        • Tenax Investigational Site
      • Málaga, Spain, 29010
        • Not yet recruiting
        • Tenax Investigational Site
      • Pamplona, Spain, 31008
        • Not yet recruiting
        • Tenax Investigational Site
      • Salamanca, Spain, 37007
        • Not yet recruiting
        • Tenax Investigational Site
      • Seville, Spain, 41009
        • Not yet recruiting
        • Tenax Investigational Site
      • Toledo, Spain, 45007
        • Not yet recruiting
        • Tenax Investigational Site
      • Valencia, Spain, 46010
        • Not yet recruiting
        • Tenax Investigational Site
      • Valencia, Spain, 46020
        • Not yet recruiting
        • Tenax Investigational Site
  • Taiwan
      • Kaohsiung City, Taiwan, 80756
        • Not yet recruiting
        • Tenax Investigational Site
      • Kaohsiung City, Taiwan, 813414
        • Not yet recruiting
        • Tenax Investigational Site
      • Taipei, Taiwan, 10449
        • Not yet recruiting
        • Tenax Investigational Site
      • Taipei, Taiwan, 110
        • Not yet recruiting
        • Tenax Investigational Site
      • Taoyuan District, Taiwan, 33305
        • Not yet recruiting
        • Tenax Investigational Site
  • United Kingdom
      • Cambridge, United Kingdom, CB233RE
        • Not yet recruiting
        • Tenax Investigational Site
      • Swindon, United Kingdom, SN36BB
        • Not yet recruiting
        • Tenax Investigational Site
  • United States
    • Alabama
      • Alexander City, Alabama, United States, 35010
        • Recruiting
        • Tenax Investigational Site
    • Florida
      • Tamarac, Florida, United States, 33321
        • Not yet recruiting
        • Tenax Investigational Site
    • Illinois
      • Mount Prospect, Illinois, United States, 60056
        • Not yet recruiting
        • Tenax Investigational Site
      • Peoria, Illinois, United States, 61636
        • Recruiting
        • Tenax Investigational Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70115-6969
        • Recruiting
        • Tenax Investigational Site
      • West Monroe, Louisiana, United States, 71291
        • Recruiting
        • Tenax Investigational Site
    • Michigan
      • Ypsilanti, Michigan, United States, 48197
        • Not yet recruiting
        • Tenax Investigational Site
    • Nevada
      • Reno, Nevada, United States, 89502
        • Recruiting
        • Tenax Investigational Site
    • New York
      • New York, New York, United States, 10032
        • Not yet recruiting
        • Tenax Investigational Site
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27101
        • Recruiting
        • Tenax Investigational Site
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18105
        • Not yet recruiting
        • Tenax Investigational Site
      • Wynnewood, Pennsylvania, United States, 19096-3450
        • Not yet recruiting
        • Tenax Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37205
        • Recruiting
        • Tenax Investigational Site
    • Texas
      • Austin, Texas, United States, 78705
        • Recruiting
        • Tenax Investigational Site
      • Dallas, Texas, United States, 75390
        • Recruiting
        • Tenax Investigational Site
      • Houston, Texas, United States, 77002
        • Recruiting
        • Tenax Investigational Site
    • Virginia
      • Norfolk, Virginia, United States, 23507-1904
        • Not yet recruiting
        • Tenax Investigational Site
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Not yet recruiting
        • Tenax Investigational Site

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men or women, ≥18 to 85 years of age
  2. NYHA Class II or III or ambulatory NYHA Class IV symptoms
  3. A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization (RHC)
  4. A qualifying baseline RHC
  5. A qualifying echocardiogram
  6. A qualifying 6-MWD
  7. A 48-hour ambulatory cardiac rhythm monitor during the Screening Period
  8. Requirements related to child bearing potential, contraception, and egg/sperm donation)

Exclusion Criteria:

  1. A diagnosis of PH WHO Groups 1, 3, 4, or 5
  2. Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
  3. Structural heart repair or replacement of the aortic valve or mitral valve (surgical or percutaneous) OR, planned valve intervention OR, the presence of significant valve disease
  4. A diagnosis of pre-existing lung disease
  5. History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product
  6. Major surgery within 60 days
  7. Prior heart, lung, or heart-lung transplants or life expectancy of <12 months
  8. History of clinically significant other diseases that may limit or complicate participation in the study

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
Intervention / Treatment
Placebo Comparator: Placebo
Matching placebo (oral)
Drug: Placebo
Matching placebo (oral)
Active Comparator: TNX-103
Oral levosimendan
Drug: TNX-103
Oral levosimendan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-Minute Walk Distance (6MWD)
Time Frame: 26 weeks
Change in 6-minute walk distance
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Worsening Events
Time Frame: 26 weeks
Number of Clinical Worsening Events
26 weeks
Clinical Worsening Event
Time Frame: 26 weeks
Time to first occurrence of a Clinical Worsening Event
26 weeks
KCCQ (Kansas City Cardiomyopathy Questionnaire) score is a standardized measure that ranges from 0 to 100, where a higher score indicates better health.
Time Frame: 26 weeks
Change in KCCQ Total Symptom Score
26 weeks
NYHA (New York Heart Association) classification assesses and categorizes a patient's physical ability and symptoms into four classes, the lower the classification, the least impact on physical activity.
Time Frame: 26 weeks
Change in NYHA Functional Class
26 weeks

Collaborators and Investigators

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

Sponsor

Tenax Therapeutics, Inc.

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)

March 3, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

December 15, 2025

First Posted (Actual)

December 17, 2025

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 12, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TNX-103-07
  • 2025-522475-28-00 (Ctis)

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.

Clinical Trials on Pulmonary Hypertension Associated With HFpEF

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe