HELP Trial Testing Levosimendan Infusion in PH-HFpEF Patients Completed

Vanessa Pataia avatar

by Vanessa Pataia |

Share this article:

Share article via email

Tenax Therapeutics has completed its Phase 2 HELP clinical trial testing levosimendan as a potential treatment for patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

Top-line trial results are expected to be available by late June.

“We are thankful for the dedicated physicians, study coordinators, and home health providers who were able to close out our study with minimal disruption from the current COVID-19 pandemic crisis,” Tony Di Tonno, Tenax CEO, said in a press release.

In people with PH-HFpEF, the heart muscles are too weak to pump blood properly, despite the fact that the heart beats normally. PH-HFpEF represents an area of very high unmet medical need with no currently approved or effective therapies.

Levosimendan is a calcium sensitizer, which was developed initially for patients with heart failure. It works to improve the contraction of the heart muscle without increasing the need for more oxygen. The therapy also has a protective effect on heart muscle, and is a vasodilator (widening blood vessels and improving blood flow and oxygenation).

The double-blind Phase 2 HELP trial (NCT03541603) enrolled PH-HFpEF patients from March 2019 through March 2020. Patients across 10 U.S. hospitals then were assigned randomly to receive either weekly infusions of levosimendan (2.5 mg/mL dose), or a placebo.

The trial had an open-label, lead-in phase that required patients to show a reduction of at least 4 mmHg in their pulmonary capillary wedge pressure (PCWP, a measure of pressure on the left side of heart) during supine (laying down) exercise, 24 hours after a single infusion of levosimendan. 

The trial initially enrolled 44 patients, of whom 37 (approximately 84%) met this criterion and moved into the double-blinded, randomized stage of the trial.

Data from 35 patients who completed the lead-in phase showed significant improvements in PCWP, with an average reduction of 7.8 mmHg.

Pulmonary arterial pressure (blood pressure in the artery that goes from the heart to the lungs) also was reduced by 4.8 mmHg on average, and right atrial pressure (blood pressure in the right atrium of the heart) was lowered by an average 5.3 mmHg.

Cardiac output — the amount of blood the heart pumps through the circulatory system in a minute — was raised by 0.4 liters/min on average, although it did not reach statistical significance.

“Based on the remarkably favorable response reported by investigators during the open label pre-randomization phase of the trial, I am hopeful the results of the randomized double-blind phase of the trial will demonstrate that levosimendan could represent a breakthrough therapy for PH-HFpEF patients,” said Stuart Rich, director of the pulmonary vascular disease program at the Bluhm Cardiovascular Institute at Northwestern University.

Rich was one of the principal investigators who helped to design and execute the HELP trial.

The primary goal of the HELP trial is to measure the change in PCWP with bicycle exercise, between the start of the study and after six weeks of weekly levosimendan infusions.

The last enrolled patient has now completed the final visit, and the process of trial data lock and analysis has started.

“We are continuing to work very closely with everyone involved in collecting and finalizing the data required to report top line data before the end of the second quarter,” Di Tonno said.

According to Tenax, no serious adverse side effects related to the therapy were reported, and only two patients did not complete the six-week study (for reasons not given in the company’s release). 

All patients who completed the trial have chosen to continue into a Phase 2 open-label extension study of the treatment (NCT03624010), in which they will receive a weekly infusion of 2.5 mg/mL levosimendan, with the goal of assessing the long-term safety and effectiveness of the treatment.

A Conversation With Rare Disease Advocates