Levosimendan for Pulmonary Hypertension with Heart Failure

(LEVEL Trial)

Recruiting at 91 trial locations

Overseen By Douglas Hay, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Tenax Therapeutics, Inc.

Disqualifiers: PH WHO Groups 1, 3, 4, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

230 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug levosimendan unique for treating pulmonary hypertension with heart failure?

Levosimendan is unique because it is a calcium-sensitizing drug that not only strengthens heart contractions but also dilates blood vessels in the lungs, potentially offering direct support to the right side of the heart, which is not addressed by current treatments. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 18-85 with WHO Group 2 PH-HFpEF, a heart condition where the left side of the heart doesn't pump well leading to high blood pressure in lungs. Participants need a specific range of walking ability and stable medication use. Pregnant or breastfeeding women can't join, and those who can have children must use effective birth control.

Inclusion Criteria

I have been diagnosed with a specific type of high blood pressure in the lungs due to heart failure.

I am a woman who can have children and have not had sex or used effective birth control for 90 days.

My heart or lung condition medication dose has been stable for over 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive oral levosimendan or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

92 weeks

Treatment Details

Interventions

• Placebo
• TNX-103

Trial Overview The study tests TNX-103 (levosimendan) against a placebo in patients with PH-HFpEF by measuring changes in their walking distance over six minutes from Day 1 to Week 12. The goal is to see if TNX-103 improves exercise capacity compared to no active treatment.

Participant Groups

Group I: TNX-103 Active Control 1 Intervention

oral levosimendan

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Tenax Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

Levosimendan is a promising treatment option for right ventricular failure in pulmonary hypertension due to its unique properties as a calcium sensitizer, which enhances heart muscle contraction and dilates blood vessels.

Currently, there are no approved therapies specifically targeting the failing right ventricle in pulmonary hypertension, highlighting the potential significance of levosimendan in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levosimendan in pulmonary hypertension and right heart failure. Hansen, MS., Andersen, A., Nielsen-Kudsk, JE.[2020]

In a rodent model of severe verapamil poisoning, levosimendan effectively increased cardiac output (CO) similar to calcium chloride (CaCl2), but did not improve blood pressure (BP) from the time of maximal toxicity.

The study suggests that levosimendan's mechanism of action, which includes peripheral vasodilation, may counteract its benefits by exacerbating hypotension during verapamil toxicity, indicating a complex interaction between these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of experimental verapamil poisoning with levosimendan utilizing a rodent model of drug toxicity. Graudins, A., Najafi, J., Rur-SC, MP.[2018]

Levosimendan is an effective treatment for acute severe decompensated heart failure, showing a 30% increase in cardiac output and significant improvements in hemodynamic response compared to placebo and dobutamine.

It is generally well tolerated with a safety profile similar to placebo, and may have a lower risk of cardiac rhythm disorders compared to dobutamine, while also potentially reducing mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levosimendan: a review of its use in the management of acute decompensated heart failure. Innes, CA., Wagstaff, AJ.[2018]

Levosimendan is a calcium-sensitizing agent that has shown effectiveness and safety in treating pulmonary arterial hypertension and pulmonary hypertension related to left heart disease, making it a promising addition to existing therapies.

This review highlights the unique properties of levosimendan, including its inotropic and pulmonary vasodilator effects, which may improve outcomes for patients suffering from this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence? Masarone, D., Kittleson, M., Pollesello, P., et al.[2023]

Levosimendan significantly enhances right ventricular contractility and overall cardiac performance in a study involving eight pigs, without affecting pulmonary vascular tone, suggesting its potential utility in right ventricular dysfunction.

The drug also improved left ventricular efficiency and cardiac output while reducing systemic vascular resistance, indicating its positive inotropic effects, although further research is needed to explore its effects in conditions of pulmonary vasoconstriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs. Leather, HA., Ver Eycken, K., Segers, P., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Levosimendan in pulmonary hypertension and right heart failure. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of experimental verapamil poisoning with levosimendan utilizing a rodent model of drug toxicity. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Levosimendan: a review of its use in the management of acute decompensated heart failure. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Use of Levosimendan in Patients with Pulmonary Hypertension: What is the Current Evidence? [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs. [2018]