Treatment of Pulmonary Arterial Hypertension Using the Aria CV Pulmonary Hypertension System (ASPIRE PH)

An Early Feasibility Study Assessing Treatment of Pulmonary Hypertension Using the Aria CV Pulmonary Hypertension System

This prospective study is a multi-center early feasibility study assessing the safety and performance of the Aria CV Pulmonary Hypertension System in patients with pulmonary hypertension and right heart dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Hypertension; Right Heart Dysfunction
• Intervention / Treatment: Device: Aria CV Pulmonary Hypertension System

Detailed Description

This clinical investigation is a prospective, non-randomized, single-arm, multi-center early feasibility study of the Aria CV Pulmonary Hypertension (PH) System implanted in patients with pulmonary hypertension (PH). The purpose of this study is to validate that the clinical use of the Aria CV PH System is safe for the patient and to evaluate its performance in treating patients with PH and right heart dysfunction.

The study will be conducted in a maximum of 20 centers in the United States and up to 30 patients will receive implants.

Patients will be evaluated at each of the following time intervals: pre-operative, implant procedure, 7-day (or discharge if earlier), and 1-, 2-, 3-, 4-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-months post index procedure. The Aria CV PH System will be assessed at each follow-up visit. The duration of the study is anticipated to last about 2 years for each patient.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caytie Longhenry; Phone Number: 651-200-4891; Email: clonghenry@ariacv.com
• Study Contact Backup: Name: Sydney Powell; Phone Number: 651-200-4891; Email: spowell@ariacv.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California - San Diego
      • Principal Investigator: Ehtisham Mahmud, MD
      • Contact: Taylor Buchalla; Email: tmbuchalla@health.ucsd.edu
      • Sub-Investigator: Ian Glenn, MD
      • Sub-Investigator: Ori Ben-Yehuda, MD
      • Sub-Investigator: Ryan Reeves, MD
      • Sub-Investigator: Lawrence Ang, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California-Los Angeles
      • Sub-Investigator: Peyman Benharash, MD
      • Sub-Investigator: Ali Nsair, MD
      • Contact: Lloyd Liang; Email: LLLiang@mednet.ucla.edu
      • Principal Investigator: Richard Channick, MD
      • Sub-Investigator: Rajan Saggar, MD
      • Sub-Investigator: Alexander Sherman, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • St. Vincent Health
      • Sub-Investigator: Amit Patel, MD
      • Principal Investigator: Ashwin Ravichandran, MD
      • Contact: Allyn (Ryn) Harker; Email: allyn.harker@ascension.org
      • Sub-Investigator: Scott Hittinger, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Olivia Vayer; Email: ovayer@bwh.harvard.edu
      • Principal Investigator: Eileen Harder, MD
      • Sub-Investigator: Aaron Waxman, MD
      • Sub-Investigator: Edgar Ross, MD
      • Sub-Investigator: Jane Leopold, MD
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Recruiting
      • Beaumont Hospital
      • Contact: Lauren Scribner, RN; Email: lauren.scribner@corewellhealth.org
      • Principal Investigator: Brian Williamson, MD
      • Sub-Investigator: Samuel Allen, DO
      • Sub-Investigator: Richard Bloomingdale, MD
      • Sub-Investigator: Ivan Hanson, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Not yet recruiting
      • University of Minnesota
      • Principal Investigator: Thenappan Thenappan, MD
      • Contact: Gretchen Peichel, RN; Email: gpeichel@umn.edu
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Louise Durst; Email: durst.louise@mayo.edu
      • Sub-Investigator: Robert Frantz
      • Principal Investigator: Adrian da Silva de Abreu
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Cornell University
      • Sub-Investigator: Maria Karas, MD
      • Principal Investigator: Evelyn Horn, MD
      • Contact: Joseph Lohmann; Email: jhl4001@med.cornell.edu
      • Sub-Investigator: Harsimran Singh, MD
      • Sub-Investigator: Berhane Worku, MD
      • Sub-Investigator: George Thomas, MD
      • Sub-Investigator: Yoshifumi Naka, MD
    • New York, New York, United States, 14627
      • Recruiting
      • University of Rochester
      • Contact: Andrew Mintz; Email: andrew_mintz@urmc.rochester.edu
      • Principal Investigator: Jim White, MD
      • Sub-Investigator: Dan Lachant, DO
      • Sub-Investigator: Fred Ling, MD
      • Sub-Investigator: Kazuhiro Hisamoto, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
      • Principal Investigator: Peter Engel, MD
      • Contact: Denise Krabbe; Email: denise.krabbe@thechristhospital.com
      • Sub-Investigator: Geoffrey Answini, MD
      • Sub-Investigator: Joseph Choo, MD
      • Sub-Investigator: Satya Shreenivas, MD
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
      • Principal Investigator: Konstantinos Boudoulas, MD
      • Sub-Investigator: David Orsinelli, MD
      • Sub-Investigator: Thura Harfi, MD
      • Contact: Annie Kellum; Email: Annie.Kellum@osumc.edu
      • Sub-Investigator: Veronica Franco, MD
      • Sub-Investigator: Mahmoud Houmsse, MD
      • Sub-Investigator: Elie Homsy, MD
    • Columbus, Ohio, United States, 43214
      • Recruiting
      • Ohio Health
      • Sub-Investigator: Steven Yakubov, MD
      • Contact: Margaret Michaud; Email: margaret.michaud@ohiohealth.com
      • Principal Investigator: Lindsay Castle, MD
      • Sub-Investigator: Anupam Basuray, MD
      • Sub-Investigator: Daniel Gorbett, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • Medical University of South Carolina
      • Contact: Renee Baxley; Email: baxleyr@musc.edu
      • Principal Investigator: Michelle Esposito, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Recruiting
      • Aurora St Luke's Medical Center
      • Sub-Investigator: Tanvir Bajwa, MD
      • Contact: Kelsey Krueger; Email: kelsey.krueger@aah.org
      • Principal Investigator: Eric Roberts, MD
      • Sub-Investigator: William Fischer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Common Inclusion Criteria:

1. 18 years of age or older.
2. Mean pulmonary artery pressure (mPAP) > 25mmHg.

3. Right heart dysfunction as evidence by at least one of the following:

   1. Tricuspid Annulus Plan Systolic Excursion (TAPSE) ≤ 16mm
   2. RV Fractional area change < 35%
   3. RV systolic velocity < 11.5 cm/s
   4. RV free wall strain < 18%
   5. Lateral tricuspid annulus peak systolic velocity (S') < 9cm/s
4. Pulmonary compliance (C) < 3.0 ml/mmHg
5. Current assessment of WHO FC III or ambulatory IV
6. Main pulmonary artery (MPA) diameter and anatomy suitable for placement of the device as defined in the Instructions For Use (IFU) and as assessed by multi-slice computed tomography (MSCT).
7. Subject is deemed appropriate for Aria CV device by the Subject Care Team at the investigation site and approved by the Eligibility Review Committee (ERC).
8. The subject has agreed to participate in the study by signing the study specific informed consent form.

9. The subject agrees to abide by device related travel restrictions.

   Unique Inclusion Criteria for WHO Group I:

10. Pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg
11. Pulmonary vascular resistance (PVR) > 3 Woods Units (WU)
12. The subject remains symptomatic despite being on a stable drug regimen of PH specific medication(s) appropriate for their PH classification for at least 90 days prior to planned index procedure.

Unique Inclusion Criteria for WHO Group II:

10. Previous diagnosis of heart failure with preserved ejection fraction (HFpEF) (ejection fraction ≥ 50%) 11. PCWP > 15 mmHg 12. PVR > 3 WU

Unique Inclusion Criteria for WHO Group III:

10. Previous diagnosis of lung disease, including but not limited to chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) including idiopathic pulmonary fibrosis (IPF) or combined emphysema with fibrosis.

11. PCWP ≤ 15mmHg 12. PVR >4 WU

Common Exclusion Criteria:

1. Diagnosis of WHO Groups 4 or 5 PH.

2. Recent clinical event(s) of any of the following:

   1. Myocardial infarction or stroke within 6 months prior to the index procedure;
   2. Sustained tachyarrhythmia (documented heart rate >110/min) within 2 months prior to the index procedure;
   3. Uncontrolled, chronic atrial fibrillation.
3. Pre-existing or requirement of emergent surgery/ intervention, or implantation of prosthetic cardiac device that, in the opinion of the investigator, may interfere with Aria CV PH System placement or function.

4. Any of the following medical history or comorbidities:

   a. History of endocarditis; b. History of unprovoked Pulmonary Embolism; c. Current renal insufficiency as demonstrated by an eGFR < 30 mL/min/1.73 m2 or end stage renal disease requiring chronic dialysis; d. Current diagnosis of scleroderma associated with: i. Any history of GI bleeding or receiving iron infusions within 2 years prior to enrollment; ii. Significant skin involvement that could compromise daily activities or the ability to receive IV medications, or sclerodactyly that causes surface ulcerations, digital ulcerations, or ulcerating calcinosis lesions.

   e. History of receiving immunosuppressant therapy as follows: i. Excluded if receiving Mycophenolate mofetil within 30 days prior to enrollment, or Rituximab within 6 months prior to enrollment, or currently receiving Prednisone at a dose > 12 mg per day at time of enrollment; ii. Excluded if any immunosuppressant other than Mycophenolate mofetil, Rituximab or Prednisone, per above.

   e. Current pulmonary veno-occlusive disease (PVOD); f. Current pulmonary capillary hemangiomatosis (PCH); g. History of clinically significant patent foramen ovale (PFO) or other inter-atrial or inter-ventricular shunt; h. History of gastric antral vascular ectasia (GAVE), gastrointestinal or intracranial bleeding which, in the opinion of the investigator, will predispose subject to major bleeding events following Aria CV device placement and warfarin anticoagulation regimen; i. Active infection requiring antibiotic therapy within two (2) weeks of procedure; j. Blood dyscrasias that may, in the opinion of investigator(s), expose subject to unacceptable procedural risks such as severe or worsening leukopenia, anemia, thrombocytopenia, untreated iron deficiency or history of bleeding diathesis or coagulopathy.

5. Anatomy is not suitable for placement of Aria CV device.

6. Right heart valve regurgitation as follows:

   1. Moderate to severe (Grade 3 or 4) pulmonary valve regurgitation;
   2. Severe (Grade 4) tricuspid valve regurgitation.

7. Hypersensitivity or contraindication to:

   1. Required medications (e.g., contrast agents, warfarin, heparin) which cannot be adequately managed;
   2. Materials in device including polyurethane, silicone, nickel, and titanium.
8. Ineligible for or refuses blood transfusion.
9. Pregnant, nursing or is planning to become pregnant in the next two years.
10. Life expectancy of less than two years.
11. Currently participating in or planning to participate in other investigational study that may interfere with the outcome of this study.
12. For subject on supplemental oxygen therapy - Subject adheres to the treatment regimen that in the opinion of the physician does not increase subject's safety.
13. Previous diagnosis of cardiac amyloidosis.

Unique Exclusion Criteria for WHO Group I:

N/A

Unique Exclusion Criteria for WHO Group II:

1. Previous diagnosis of idiopathic hypertrophic subaortic stenosis (IHSS, also known as hypertrophic obstructive cardiomyopathy - HOCM).
2. Untreated severe aortic or mitral stenosis
3. Diagnosis of heart failure with reduced ejection fraction (HFrEF)
4. Previous diagnosis of nonobstructive hypertrophic cardiomyopathy.

Unique Exclusion Criteria for WHO Group III:

N/A

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aria CV Pulmonary Hypertension System; Treatment with the Aria CV Pulmonary Hypertension System	Device: Aria CV Pulmonary Hypertension System; The Aria CV PH System is indicated for the treatment of adult patients diagnosed with Pulmonary Hypertension in World Health Organization (WHO) Groups I, II, and III who remain symptomatic despite treatment with optimal medical therapy.; Other Names: Aria CV PH System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint is the incidence of investigational device- or procedure-related serious adverse events (SAEs).	The primary safety endpoint is the incidence of investigational device- or procedure-related serious adverse events through 30 days post-index procedure.	30 days post-implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Device Implantation Success	Incidence of successful implantation of the Aria CV device defined as follows: Absence of investigational device or procedure-related patient death within 7 days post index procedure based on Data Safety Monitoring Board (DSMB) adjudication;; Correct positioning of the Aria CV device implantable components at the targeted locations upon completion of index procedure based on imaging; and; Aria CV balloon inflates and deflates responding to cyclic pressure changes in the pulmonary artery at time of index procedure, based on imaging.	7 days post-implant
Changes in World Health Organization (WHO) Functional Class	Changes in WHO Functional Class from baseline to 6-month.	6 months post-implant
Changes in 6-Minute Walk Distance	Changes in the 6-minute walk distance from baseline to 6-month.	6 months post-implant
Changes in Modified Borg Dyspnea Score (MBS)	Changes in MBS from baseline to 6-months. MBS is a measure of breathlessness during exercise that ranges from 0 to 10, where 0 is no breathlessness and 10 is maximal breathlessness.	6 months post-implant
Changes in biomarker N-terminal pro hormone BNP (NT-pro-BNP)	Change in N-terminal pro hormone BNP (NT-pro-BNP) from baseline to 6-months.	6 months post-implant
Changes in REVEAL Score	Changes in REVEAL Score 2.0 from baseline to 6-months. The REVEAL 2.0 is a risk calculator for PAH patients that ranges from 0 (lowest risk) to 22 (highest risk).	6 months post-implant
Changes in quality of life as measured by the Living with Pulmonary Hypertension (LPH) questionnaire score	Changes in quality of life from baseline to 6-months as measured by the LPH total score. The Living with Pulmonary Hypertension (LPH) questionnaire has 21 questions each scored on a 6-point scale ranging from 0 (no) to 5 (very much). The LPH total score, calculated by summing scores for the 21 individual questions, ranges from 0 (best) to 105 (worst).	6-months post-implant
Changes in quality of life as measured by the emPHasis-10 questionnaire score	Changes in quality of life from baseline to 6-months as measured by the emPHasis-10 questionnaire score which assesses breathlessness, fatigue, confidence and control. The total score ranges from 0 to 50 with higher scores indicating poorer quality of life.	6-months post-implant
Incidence of Serious Adverse Events	Safety will be evaluated by assessing the incidence of device and/or procedure related SAEs from device implant through last follow up.	24 months post-implant
Changes in pulmonary vascular resistance (PVR)	Changes in PVR (Woods unit) as measured by right heart catheterization from baseline to 6 months.	6 months post-implant
Changes in pulmonary artery pressures (PAPs)	Changes in PAPs (mmHg) as measured by right heart catheterization from baseline to 6 months.	6 months post-implant
Changes in pulmonary capillary wedge pressure (PCWP)	Changes in PCWP (mmHg) as measured by right heart catheterization from baseline to 6 months.	6 months post-implant
Changes in pulmonary arterial compliance	Changes in pulmonary arterial compliance (L/mmHg) as measured by right heart catheterization from baseline to 6 months.	6 months post-implant
Changes in cardiac output (CO) from baseline	Changes in cardiac output (L/Min) as measured by right heart catheterization from baseline to 6 months.	6 months post-implant
Changes in right heart function	Changes in right heart function as measured by echocardiographic imaging.	6 months post-implant

Collaborators and Investigators

• Sponsor: Aria CV, Inc
• Investigators: Principal Investigator: Aaron Waxman, M.D.,Ph.D., Brigham and Women's Hospital

Publications and helpful links

Helpful Links

• Information about the Aria CV Pulmonary Hypertension System

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Lung Disease; Pulmonary Disease; Pulmonary Artery; Right Heart Dysfunction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: ASPIREPH202001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes