The CONFORM Pivotal Trial

• ClinicalTrials.gov Identifier: NCT05147792
• Recruitment Status: Suspended
• First Posted: December 7, 2021
• Last Update Posted: May 3, 2024
• Sponsor: Conformal Medical, Inc
• Information provided by (Responsible Party): Conformal Medical, Inc

Tracking Information

• First Submitted Date: November 24, 2021
• First Posted Date: December 7, 2021
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: May 26, 2022
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2022)

• Procedure-related complications, all-cause death, major bleeding [ Time Frame: 12 months ]
  The primary safety endpoint is a composite of 1) major procedure-related complications including a) cardiac perforation, b) pericardial effusion requiring drainage, c) ischemic stroke, d) device embolization, and e) major vascular complications, or 2) major bleeding, or 3) all-cause death
• Ischemic stroke and systemic embolism [ Time Frame: 18 months ]
  The primary effectiveness endpoint is a composite of ischemic stroke and systemic embolism through 18 months.

Original Primary Outcome Measures (submitted: November 24, 2021)

• Procedure-related complications, all-cause death, major bleeding [ Time Frame: 12 months ]
  The primary safety endpoint is a composite of procedure-related complications, or all cause death, or major bleeding through 12 months.
• Ischemic stroke and systemic embolism [ Time Frame: 18 months ]
  The primary effectiveness endpoint is a composite of ischemic stroke and systemic embolism through 18 months.

Current Secondary Outcome Measures (submitted: August 16, 2022)

• All Cause Mortality [ Time Frame: 18 months ]
  A secondary safety endpoint is all-cause mortality including cardiovascular through 18 months
• Myocardial Infarction [ Time Frame: 7 days ]
  A secondary safety endpoint is myocardial infarction evaluated through 7 days post-procedure
• Neurologic Events [ Time Frame: 45 days ]
  A secondary safety endpoint is neurologic events including stroke (ischemic and hemorrhagic) and TIA
• Closure Success [ Time Frame: 12 months ]
  A secondary performance and efficacy endpoint is closure success at 12 months based upon each of the following criteria: a) demonstration of peri-device flow </=5 mm, and b) demonstration of peri-device flow </=3 mm

Original Secondary Outcome Measures (submitted: November 24, 2021)

• Major procedure-related complications [ Time Frame: 45 days ]
  A composite of cardiac perforation, pericardial effusion requiring drainage, ischemic stroke, device embolization, and major vascular complications through 45 days.
• Major safety events [ Time Frame: 18 months ]
  A composite of all-cause mortality, overt CNS injury (NeuroARC defined), and major bleeding (BARC Type 3-5) through 18 months.
• Closure success [ Time Frame: 45 days ]
  Closure or peri-device residual leak <5 mm in width on transesophageal echocardiogram (TEE).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The CONFORM Pivotal Trial
• Official Title: An Evaluation of the Safety and Effectiveness of the Conformal CLAAS System for Left Atrial Appendage Occlusion
• Brief Summary: The CLAAS® device will be evaluated for safety and efficacy by establishing its performance is non-inferior to the commercially available WATCHMAN® and Amulet™ left atrial appendage closure devices in patients with non-valvular atrial fibrillation. Patients who are eligible for the trial will be randomized to receive either the CLAAS device or the WATCHMAN or Amulet™ devices and will be followed for 5 years after device implant.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Atrial Fibrillation
• Stroke

Intervention

• Device: CLAAS
  CLAAS
• Device: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder
  WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder

Study Arms

• Experimental: CLAAS
  Transcatheter left atrial occluder
  Intervention: Device: CLAAS
• Active Comparator: WATCHMAN / Amulet
  Transcatheter left atrial occluder
  Intervention: Device: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: August 30, 2022): 1600
• Original Estimated Enrollment (submitted: November 24, 2021): 1400
• Estimated Study Completion Date: August 2030
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or non-pregnant female aged ≥18 years
2. Documented non-valvular AF (paroxysmal, persistent, or permanent)
3. High risk of stroke or systemic embolism, defined as CHADS2 score of >2 or CHA2DS2-VASc score of ≥ 3
4. Has an appropriate rationale to seek a non-pharmacologic alternative to long-term oral anticoagulation
5. Deemed by the site investigator to be suitable for short term oral anticoagulation therapy but deemed less favorable for long-term oral anticoagulation therapy.
6. Deemed appropriate for LAA closure by the site investigator and a clinician not a part of the procedural team using a shared decision-making process in accordance with standard of care
7. Able to comply with the protocol-specified medication regimen and follow-up evaluations
8. The patient (or legally authorized representative, where allowed) has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate institutional review board (IRB)/Regional Ethics Board (REB)/Ethics Committee (EC).

Exclusion Criteria:

1. Pregnant or nursing patients and those who plan pregnancy in the period up to one year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure.
2. Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., prior atrial septal defect [ASD] or high-risk patent foramen ovale [PFO], surgical repair or implanted closure device, or obliterated or ligated left atrial appendage)
3. Atrial fibrillation that is defined by a single occurrence or that is transient or reversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
4. A medical condition (other than atrial fibrillation) that mandates long-term oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or mechanical heart valve)
5. History of bleeding diathesis or coagulopathy, or patients in whom antiplatelet and/or anticoagulant therapy is contraindicated
6. Documented active systemic infection
7. Symptomatic carotid artery disease (defined as >50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is <50% stenosis noted at the site of prior treatment
8. Recent (within 30 days of index procedure) or planned (within 60 days post-procedure) cardiac or non-cardiac interventional or surgical procedure
9. Recent (within 30 days of index procedure) stroke or transient ischemic attack
10. Recent (within 30 days of index procedure) myocardial infarction
11. Vascular access precluding delivery of implant with catheter-based system
12. Severe heart failure (New York Heart Association Class IV)
13. Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any mechanical valve implant
14. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation)
15. Platelet count <75,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <3,000 cells/mm3
16. Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium) that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated
17. Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
18. Unable to undergo general anesthesia
19. Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years
20. A condition which precludes adequate transesophageal echocardiographic assessment

Echo exclusion criteria:

1. Left atrial appendage anatomy which cannot accommodate a commercially available control device or the CLAAS device per manufacturer IFU (e.g., the anatomy and sizing must be appropriate for both devices to be enrolled in the trial)
2. Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus, as visualized by TEE prior to implant
3. Left ventricular ejection fraction (LVEF) <30%
4. Moderate or large circumferential pericardial effusion >10 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology
5. Atrial septal defect that warrants closure
6. High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion >15 mm or length > 15 mm) or large shunt (early [within 3 beats] and/or substantial passage of bubbles, e.g., >20)
7. Moderate or severe mitral valve stenosis (mitral valve area <1.5 cm2)
8. Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
9. Evidence of cardiac tumor

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Georgia, United States, Uzbekistan

Administrative Information

• NCT Number: NCT05147792
• Other Study ID Numbers: 21-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Conformal Medical, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Conformal Medical, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: William Gray, M.D.; Lankenau Heart Institute
• Principal Investigator: Shephal Doshi, M.D.; Pacific Heart Institute

• PRS Account: Conformal Medical, Inc
• Verification Date: May 2024