Pulmonary Hypertension Associated With HFpEFPhase 3LEVEL-2NCT07288398
LEVEL-2: LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF-2
A Phase 3 study testing TNX-103 in people with Pulmonary Hypertension Associated With HFpEF, run by Tenax Therapeutics, Inc. at 140 sites in 15 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Pulmonary Hypertension Associated With HFpEF
- What is being tested?
- TNX-103
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 540 participants
- Where
- 140 sitesin 15 countries
- Study dates
- 3 Mar 2026to 30 Jun 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women, ≥18 to 85 years of age
- NYHA Class II or III or ambulatory NYHA Class IV symptoms
- A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization (RHC)
- A qualifying baseline RHC
- A qualifying echocardiogram
- A qualifying 6-MWD
- A 48-hour ambulatory cardiac rhythm monitor during the Screening Period
- Requirements related to child bearing potential, contraception, and egg/sperm donation)
Who cannot join
- A diagnosis of PH WHO Groups 1, 3, 4, or 5
- Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
- 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
- A diagnosis of pre-existing lung disease
- History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product
- Major surgery within 60 days
- Prior heart, lung, or heart-lung transplants or life expectancy of <12 months
- History of clinically significant other diseases that may limit or complicate participation in the study
Trial locations and contacts
140 sites in 15 countries.
140 sites in 15 countries
United States45 sites
Tenax Investigational Site
Alexander City, Alabama, 35010
Tenax Investigational Site
Allentown, Pennsylvania, 18105
Tenax Investigational Site
Ann Arbor, Michigan, 48109
Tenax Investigational Site
Athens, Georgia, 30606
Tenax Investigational Site
Atlanta, Georgia, 30322
Tenax Investigational Site
Austin, Texas, 78705
Tenax Investigational Site
Boston, Massachusetts, 02114-2621
Tenax Investigational Site
Charleston, South Carolina, 29425
Tenax Investigational Site
Charlottesville, Virginia, 22908
Tenax Investigational Site
Chicago, Illinois, 60611-4494
Tenax Investigational Site
Chicago, Illinois, 60637
Tenax Investigational Site
Cleveland, Ohio, 44195-0001
Tenax Investigational Site
Columbus, Ohio, 43210
Tenax Investigational Site
Dallas, Texas, 75390
Tenax Investigational Site
Durham, North Carolina, 27710
Tenax Investigational Site
El Paso, Texas, 79905-2707
Tenax Investigational Site
Houston, Texas, 77030-2342
Tenax Investigational Site
Indianapolis, Indiana, 46260
Tenax Investigational Site
Kansas City, Missouri, 64111
Tenax Investigational Site
Madison, Wisconsin, 53706
Tenax Investigational Site
Marshfield, Wisconsin, 54449
Tenax Investigational Site
Minneapolis, Minnesota, 55455
Tenax Investigational Site
Mount Prospect, Illinois, 60056
Tenax Investigational Site
Nashville, Tennessee, 37205
Tenax Investigational Site
New Orleans, Louisiana, 70115-6969
Tenax Investigational Site
New York, New York, 10021
Tenax Investigational Site
New York, New York, 10032
Tenax Investigational Site
Norfolk, Virginia, 23507-1904
Tenax Investigational Site
Omaha, Nebraska, 68198
Tenax Investigational Site
Peoria, Illinois, 61636
Tenax Investigational Site
Pittsburgh, Pennsylvania, 15212
Tenax Investigational Site
Reno, Nevada, 89502
Tenax Investigational Site
Rochester, Minnesota, 55905
Tenax Investigational Site
Rochester, New York, 14617
Tenax Investigational Site
Sacramento, California, 95816
Tenax Investigational Site
San Francisco, California, 94143
Tenax Investigational Site
Seattle, Washington, 98122
Tenax Investigational Site
St Louis, Missouri, 63136
Tenax Investigational Site
Stanford, California, 94305-5208
Tenax Investigational Site
Torrance, California, 90502
Tenax Investigational Site
Tucson, Arizona, 85724
Tenax Investigational Site
West Monroe, Louisiana, 71291
Tenax Investigational Site
Winston-Salem, North Carolina, 27101
Tenax Investigational Site
Wynnewood, Pennsylvania, 19096-3450
Tenax Investigational Site
Ypsilanti, Michigan, 48197
Spain15 sites
Tenax Investigational Site
Barcelona, 08003
Tenax Investigational Site
Barcelona, 08035
Tenax Investigational Site
Barcelona, 08036
Tenax Investigational Site
Lugo, 27003
Tenax Investigational Site
Madrid, 28041
Tenax Investigational Site
Madrid, 28046
Tenax Investigational Site
Madrid, 28055
Tenax Investigational Site
Málaga, 29010
Tenax Investigational Site
Marbella, 29603
Tenax Investigational Site
Pamplona, 31008
Tenax Investigational Site
Salamanca, 37007
Tenax Investigational Site
Seville, 41009
Tenax Investigational Site
Toledo, 45007
Tenax Investigational Site
Valencia, 46010
Tenax Investigational Site
Valencia, 46020
Italy10 sites
Tenax Investigational Site
Acquaviva delle Fonti, 70021
Tenax Investigational Site
Bergamo, 24127
Tenax Investigational Site
Messina, 98125
Tenax Investigational Site
Milan, 20132
Tenax Investigational Site
Milan, 20138
Tenax Investigational Site
Milan, 20149
Tenax Investigational Site
Pavia, 27100
Tenax Investigational Site
Pisa, 56126
Tenax Investigational Site
Roma, 00168
Tenax Investigational Site
Rozzano, 20089
Argentina9 sites
Tenax Investigational Site
Buenos Aires, Buenos Aires F.D., 1280
Tenax Investigational Site
Buenos Aires, C1180AAX
Tenax Investigational Site
Buenos Aires, C1428ART
Tenax Investigational Site
Córdoba, 5000
Tenax Investigational Site
Córdoba, X5016KET
Tenax Investigational Site
Corrientes, W3400AMZ
Tenax Investigational Site
San Juan Bautista, Buenos Aires, 1888
Tenax Investigational Site
San Luis, D5702JRS
Tenax Investigational Site
Santa Fe, S2002KDS
Brazil7 sites
Tenax Investigational Site
Belo Horizonte, Minas Gerais, 30220
Tenax Investigational Site
Curitiba, Paraná, 80215-901
Tenax Investigational Site
Goiânia, Goiás, 74605
Tenax Investigational Site
Porto Alegre, Rio Grande do Sul, 90020-090
Tenax Investigational Site
Porto Alegre, Rio Grande do Sul, 90035-903
Tenax Investigational Site
Ribeirão Preto, São Paulo, 14026-020
Tenax Investigational Site
Salvador, Estado de Bahia, 40170-130
Germany7 sites
Tenax Investigational Site
Bad Bevensen, 29549
Tenax Investigational Site
Bad Nauheim, 61231
Tenax Investigational Site
Berlin, 12683
Tenax Investigational Site
Dresden, 01307
Tenax Investigational Site
Hamburg, 20251
Tenax Investigational Site
Jena, 07747
Tenax Investigational Site
Mainz, 55131
Austria6 sites
Tenax Investigational Site
Braunau am Inn, 5280
Tenax Investigational Site
Graz, 8036
Tenax Investigational Site
Klagenfurt, 9020
Tenax Investigational Site
Sankt Pölten, 3100
Tenax Investigational Site
Vienna, State of Vienna, 1090
Tenax Investigational Site
Vienna, 1100
Bulgaria6 sites
Tenax Investigational Site
Burgas, 8000
Tenax Investigational Site
Pleven, 5800
Tenax Investigational Site
Sofia, 1309
Tenax Investigational Site
Sofia, 1407
Tenax Investigational Site
Sofia, 1431
Tenax Investigational Site
Sofia, 1750
France6 sites
Tenax Investigational Site
Le Kremlin-Bicêtre, 94270
Tenax Investigational Site
Montpellier, 34295
Tenax Investigational Site
Nantes, 44007
Tenax Investigational Site
Nice, 06001
Tenax Investigational Site
Pau, 64000
Tenax Investigational Site
Poitiers, 86000
South Korea6 sites
Tenax Investigational Site
Cheongju-si, 28644
Tenax Investigational Site
Gwangju, 61469
Tenax Investigational Site
Incheon, 21565
Tenax Investigational Site
Seoul, 03080
Tenax Investigational Site
Seoul, 08308
Tenax Investigational Site
Wŏnju, 26426
Taiwan6 sites
Tenax Investigational Site
Kaohsiung City, 80756
Tenax Investigational Site
Kaohsiung City, 813414
Tenax Investigational Site
Tainan, 71004
Tenax Investigational Site
Taipei, 10449
Tenax Investigational Site
Taipei, 110
Tenax Investigational Site
Taoyuan, 33305
United Kingdom6 sites
Tenax Investigational Site
Cambridge, CB233RE
Tenax Investigational Site
Glasgow, G81 4HS
Tenax Investigational Site
London, SW3 6NP
Tenax Investigational Site
London, W12 0HS
Tenax Investigational Site
Sheffield, S10 2JF
Tenax Investigational Site
Swindon, SN36BB
Hungary4 sites
Tenax Investigational Site
Budapest, 1122
Tenax Investigational Site
Budapest, 1134
Tenax Investigational Site
Debrecen, 4032
Tenax Investigational Site
Szeged, 6275
Poland4 sites
Tenax Investigational Site
Grodzisk Mazowiecki, 05-825
Tenax Investigational Site
Poznan, 61848
Tenax Investigational Site
Wroclaw, 50556
Tenax Investigational Site
Wroclaw, 50891
Czechia3 sites
Tenax Investigational Site
Ostrava, 72880
Tenax Investigational Site
Prague, 10034
Tenax Investigational Site
Prague, 15006
About this study
Official title: 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.
Read the 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.
- Being tested
- TNX-103, Placebo
- Keywords
- PH-HFpEF, levosimendan, HFpEF, Heart Failure, Pulmonary Hypertension Group 2
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNX-103Drug
Oral levosimendan
PlaceboDrug
Matching placebo (oral)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo (oral) Receives: Drug: Placebo |
| TNX-103 | Active comparator | Oral levosimendan Receives: Drug: TNX-103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-Minute Walk Distance (6MWD)
Change in 6-minute walk distance
Measured: 26 weeks
Secondary outcomes (4)
KCCQ (Kansas City Cardiomyopathy Questionnaire) score is a standardized measure that ranges from 0 to 100, where a higher score indicates better health.
Change in KCCQ Total Symptom Score
Measured: 26 weeks
Clinical Worsening Events
Number of Clinical Worsening Events
Measured: 26 weeks
Clinical Worsening Event
Time to first occurrence of a Clinical Worsening Event
Measured: 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.
Change in NYHA Functional Class
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2025
- Study start3 Mar 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Hypertension Associated With HFpEFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tenax Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07288398
- Sponsor's protocol ID
- TNX-103-07
- Other IDs
- 2025-522475-28-00, 2025
- Acronym
- LEVEL-2
- Status last verified
- Oct 2026
- First submitted
- 15 Dec 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction
- ClinicalTrials.gov ID
- NCT07288398
- Acronym / sponsor ID
- LEVEL-2 / TNX-103-07
- Keywords
- PH-HFpEF, levosimendan, HFpEF, Heart Failure, Pulmonary Hypertension Group 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Tenax Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Mar 2026 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 17 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo (oral) |
| TNX-103 | Active comparator | Drug: TNX-103Oral levosimendan |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men or women, ≥18 to 85 years of age
- NYHA Class II or III or ambulatory NYHA Class IV symptoms
- A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization (RHC)
- A qualifying baseline RHC
- A qualifying echocardiogram
Key exclusion criteria (8 listed)
- A diagnosis of PH WHO Groups 1, 3, 4, or 5
- Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
- 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
- A diagnosis of pre-existing lung disease
- History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNX-103Oral levosimendan | Drug | TNX-103 |
| PlaceboMatching placebo (oral) | Drug | Placebo |
Primary outcome
6-Minute Walk Distance (6MWD)
Time frame: 26 weeks
Change in 6-minute walk distance
4 secondary outcomes
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
Clinical Worsening Events
Time frame: 26 weeks
Clinical Worsening Event
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Pulmonary Hypertension Associated With HFpEF
Enrolling by invitationPhase 3
Long-Term Open-Label Extension Study of Oral Levosimendan
Pulmonary Hypertension Associated With HFpEF
RecruitingEarly Phase 1
Percutaneous Pulmonary Artery Denervation (PADN) for the Treatment of Pulmonary Hypertension After Transcatheter Mitral Valve Edge-to-Edge Repair (M-TEER): A Prospective Cohort Study
Pulmonary Hypertension, Pulmonary Hypertension Associated With HFpEF
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
140 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TNX-103 in people with Pulmonary Hypertension Associated With HFpEF, run by Tenax Therapeutics, Inc. at 140 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 140 sites in United States, Spain, Italy, Argentina, Brazil and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-Minute Walk Distance (6MWD) (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.