Treatment for pulmonary arterial hypertension using a new device

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

This study is testing a new device to see if it can safely help people with pulmonary hypertension and right heart problems feel better.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Aria CV, Inc (Industry-sponsored)
• Drugs / interventions: Rituximab, Prednisone
• Locations: 12 sites (La Jolla, California and 11 other locations)
• Trial ID: NCT04555161 on ClinicalTrials.gov

What this trial studies

This is a multi-center early feasibility study evaluating the safety and performance of the Aria CV Pulmonary Hypertension System in patients suffering from pulmonary hypertension and right heart dysfunction. The study involves implanting the device in up to 30 patients across 20 centers in the United States. Participants will be monitored at various intervals post-implantation to assess the device's effectiveness and safety over a two-year period. The goal is to validate the clinical use of this system for treating pulmonary hypertension.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed pulmonary hypertension and evidence of right heart dysfunction.

Not a fit: Patients with pulmonary artery pressure below the threshold or those not meeting the specific criteria for right heart dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of pulmonary arterial hypertension and enhance patients' quality of life.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in treating pulmonary hypertension with device-based interventions.

Eligibility criteria

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

Where this trial is running

La Jolla, California and 11 other locations

• University of California - San Diego — La Jolla, California, United States (Withdrawn)
• University of California-Los Angeles — Los Angeles, California, United States (Recruiting)
• St. Vincent Health — Indianapolis, Indiana, United States (Recruiting)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Cornell University — New York, New York, United States (Recruiting)
• University of Rochester — New York, New York, United States (Recruiting)
• The Christ Hospital — Cincinnati, Ohio, United States (Withdrawn)
• Ohio Health — Columbus, Ohio, United States (Recruiting)
• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)
• Aurora St Luke's Medical Center — Milwaukee, Wisconsin, United States (Withdrawn)

Study contacts

• Principal investigator: Ashwin Ravichandran, M.D. — Ascension Health
• Study coordinator: Caytie Longhenry

Conditions Pulmonary Arterial Hypertension; Pulmonary Hypertension; Right Heart Dysfunction; Pulmonary Disease; Pulmonary Artery; Lung Disease