Endotronix Receives IDE Approval for Cordella Sensor PROACTIVE-HF 2 Trial

October 9, 2023—Endotronix, Inc. announced it has received FDA investigational device exemption approval for the PROACTIVE-HF 2 multicenter study, which will evaluate the company’s Cordella sensor for pulmonary artery (PA) pressure–guided therapy in the treatment of patients with heart failure (HF).

The company noted that the PROACTIVE-HF 2 study design was presented at HFSA 2023, the annual scientific meeting of the Heart Failure Society of America held October 6-9 in Cleveland, Ohio.

Additionally, the company announced that 12-month substudy data from its initial pivotal PROACTIVE-HF trial were presented at HFSA 2023.

According to Endotronix, the dual-arm PROACTIVE-HF 2 trial aims to expand access to New York Heart Association (NYHA) class II HF patients and support efficient and scalable remote patient management with a clinician-directed, patient self-management strategy.

PROACTIVE-HF 2 is a prospective, open-label, randomized controlled clinical trial that will enroll up to 1,500 patients in the United States and Europe. The first patient is expected to be enrolled later this year.

The randomized arm will assess the safety and efficacy of PA pressure–guided therapy using Cordella in NYHA class II patients at risk for congestion. In both cohorts, patients and clinicians will have access to daily trended telehealth data (ie, blood pressure, heart rate, weight), and the treatment cohort will also have access to daily PA pressure data.

The study will evaluate safety and efficacy, using a compositive first HF event or death rate, for up to 24 months.

The single-arm study will assess the impact of clinician-directed patient self-management at home in NYHA class III HF patients at risk for poor outcomes using a 12-month endpoint for safety and incidence of HF hospitalization or death.

Both arms will collect data on secondary endpoints, including changes in right ventricular function in relation to PA pressure and patient engagement.

Lynne W. Stevenson, MD, HF specialist at Vanderbilt University Medical Center in Nashville, Tennessee, is Global Principal Investigator of PROACTIVE-HF 2.

“The evidence in favor of PA pressure–guided therapy for NYHA class III HF patients has been consistently validated over the last 15 years,” commented Dr. Stevenson in the company’s press release. “However, questions remain as to the therapy benefit in NYHA class II patients and how to best scale effective remote HF management.”

Dr. Stevenson continued, “The randomized arm of PROACTIVE-HF 2 will be the first study to compare PA pressure–guided therapy to a telehealth control arm. The single-arm cohort evaluates the power of engaged patients and subsequent impact on outcomes. Together, these studies help us better understand the impact of pulmonary hypertension on right ventricular function over time and provide guidance on how to scale this important therapy with patient engagement.”

In the pivotal PROACTIVE-HF trial, the 12-month substudy data presented at HFSA meeting demonstrated a low HF hospitalization rate of 0.34% at 12 months in NYHA class III HF patients.

The company noted that in December 2021, the prospective, multicenter pivotal PROACTIVE-HF trial was redesigned from a randomized controlled trial in which patients and providers in a control arm were blinded to PA pressure values to a single-arm study where both groups had access to patient data.

Endotronix announced FDA approval of the shift on January 5, 2022. On April 4, 2023, the company announced completion of enrollment in the pivotal trial, which started in February 2020.

The data for 63 former control arm patients were evaluated before and during the 12-month period after the unblinding, demonstrating significant improvements in mean PA pressure (mPAP) and outcomes, as well as strong patient interest in having access to PA pressure data.

The data showed the following:

• In the unblinded period, average seated mPAP for patients above target (> 20 mm Hg) decreased significantly (28.1 mm Hg vs 23.6 mm Hg; P = .03).
• 12-month unblinded HF hospitalization rate was significantly lower than the 12 months before implantation (0.3 ± 0.9 vs 1.3 ± 0.9; P < .0001).
• 78% of patients made lifestyle changes based on their mPAP trends.
• 86% of patients rated a positive impact of PA pressure management on their health.

The company noted that the presentation of these data coincides with the announcement that the PROACTIVE-HF study has completed its primary endpoint follow-up period. The data are being prepared for premarket approval submission to the FDA by the end of the year, with data presentation in the first half of 2024.

Endotronix advised that the Cordella PA pressure sensor system is an investigational device and is not currently approved for clinical use in any geography. The Cordella HF system, without the sensor, is available for commercial use in the United States and European Union.