LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05983250

Acronym

LEVEL

Enrollment

230

Registered

2023-08-09

Start date

2024-01-10

Completion date

2028-10-30

Last updated

2026-07-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Hypertension

Keywords

HFpEF, Pulmonary hypertension group 2, PH-HFpEF, Heart Failure

Brief summary

This study will evaluate the efficacy of TNX-103 (oral levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to Week 12).

Detailed description

This is a Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will provide written informed consent prior to completing any study procedures. Upon meeting all eligibility criteria, patients will continue to the 12-week randomized, double-blind treatment phase. Approximately 230 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan or placebo All randomized subjects will have the option to enter the 92-week OLE following the completion of all study events at Week 12.

Interventions

DRUGTNX-103

oral levosimendan 1 mg

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

The blind is maintained by the use of a matching placebo.

Intervention model description

Double blind, randomized, placebo controlled

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

Inclusion criteria

1. Men or women, greater than or equal to18 to 85 years of age. 2. NYHA Class II or III or NYHA class IV symptoms. 3. A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics 4. Qualifying Baseline RHC. 5. Qualifying echocardiogram 6. 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.

Design outcomes

Primary

Measure	Time frame
Change in Six-minute walk distance	12 weeks

Secondary

Measure	Time frame	Description
KCCQ	12 weeks	Change in KCCQ
Clinical Worsening Events	12 weeks	—
Change in NT-proBNP	12 weeks	Decreases in NT-proBNP may indicate an improvement in symptoms
Change NYHA functional class	12 weeks	On a scale of I-IV. Lower scores may indicate improvement in symptoms

Countries

Canada, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 25, 2026