DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE)

• ClinicalTrials.gov Identifier: NCT05701917
• Recruitment Status: Recruiting
• First Posted: January 27, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Inari Medical
• Information provided by (Responsible Party): Inari Medical

Tracking Information

• First Submitted Date: January 6, 2023
• First Posted Date: January 27, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: January 6, 2023
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2023)

Composite clinical endpoint constructed as a win ratio, a hierarchy of the following: [ Time Frame: 180 Days (+-14 Days) ]

1. Occurrence of treatment failure or therapy escalation
2. Assessment of PTS severity, as defined by the Villalta scale

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2023)

• Composite clinical endpoint constructed as a win ratio, a hierarchy of the following: [ Time Frame: 10 Days (+- 3 Days) ]
  1. Vessel compressibility assessed by duplex ultrasound
  2. Pain as assessed by the NPRS
  3. An improvement of edema as assessed by leg calf circumference measurements
• Assessment of PTS Severity: [ Time Frame: 180 Days (+-14 Days) ]
  a. Assessment of PTS severity, as defined by the Villalta scale

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis
• Official Title: DEFIANCE - ClotTriever® Thrombectomy System vs. Anticoagulation Alone for Treatment of Deep Vein Thrombosis
• Brief Summary: This study is a prospective, multicenter, randomized controlled trial of an interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm) versus conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm) in the treatment of subjects with symptomatic unilateral iliofemoral DVT. The study will collect data on demographics, comorbidities, details from the DVT diagnosis and treatment, and clinical outcomes through the 6-month follow up visit.
• Detailed Description: The study will compare the clinical outcomes of patients treated with an interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm) versus conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm) in the treatment of symptomatic unilateral iliofemoral DVT. Up to 300 subjects will be enrolled and randomized. All subjects who sign informed consent and who meet all of the inclusion criteria and none of the exclusion criteria will be randomized (1:1, ClotTriever Intervention Arm or Conservative Medical Management Arm).
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Venous Thromboembolism
• Deep Venous Thrombosis
• Post-Thrombotic Syndrome

Intervention

• Device: ClotTriever System
  Mechanical thrombectomy
• Drug: Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc.
  Anticoagulants are a group of medications that decrease your blood's ability to clot.

Study Arms

• Active Comparator: Interventional
  Interventional strategy using the ClotTriever System to achieve and maintain vessel patency (ClotTriever Intervention Arm).
  Intervention: Device: ClotTriever System
• Active Comparator: Conservative Medical Management
  Conservative medical management using anticoagulation therapy alone (Conservative Medical Management Arm).
  Intervention: Drug: Commercially available/market approved anticoagulation medication including but not limited to: Heparin Sodium, Coumadin, Rivaroxaban, Apixaban, etc.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2023): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2025
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Proximal lower extremity unilateral DVT involving at least the common femoral, external iliac, or common iliac veins, alone or in combination
• Symptom onset within 12 weeks of enrollment in the study
• Significant symptoms, as defined by a Villalta score > 9
• Willing and able to provide informed consent

Exclusion Criteria

• Bilateral iliofemoral DVT
• Prior venous stent in the target venous segment
• IVC aplasia/hypoplasia or other congenital anatomic anomalies of the IVC or iliac veins
• IVC filter in place at the time of enrollment
• Limb-threatening circulatory compromise (e.g., phlegmasia)
• Clot in transit including IVC thrombus presenting as extension of >2cm into the IVC from the CIV
• Symptomatic PE with right heart strain where the physician judges that a DVT intervention is inappropriate at this time.
• Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement
• Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• Severe allergy to iodinated contrast agents that cannot be mitigated
• Hemoglobin < 8.0 g/dL, INR > 1.7 before warfarin was started, or platelets < 50,000/µl which cannot be corrected prior to enrollment
• Severe renal impairment (estimated GFR < 30 ml/min) in patients who are not yet on dialysis
• Inability to provide therapeutic anticoagulation per Investigator discretion
• Uncontrolled severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105mmHg)
• Recently (< 30 days) had DVT interventional procedure
• Subject is participating in another study that may interfere with this study
• Life expectancy < 6 months or chronic non-ambulatory status
• Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., contraindication to use of ClotTriever per local approved labeling, compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments)
• Subject has previously completed or withdrawn from this study
• Patient unwilling or unable to conduct the follow up visits per protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Christine Wills; 6027992920; christine.wills@inarimedical.com

Contact: Chris Ottaviano; 6096344571; chris.ottaviano@inarimedical.com

• Listed Location Countries: Finland, Germany, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT05701917
• Other Study ID Numbers: 22-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Inari Medical
• Original Responsible Party: Same as current
• Current Study Sponsor: Inari Medical
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Steven Abramowitz, MD; MedStar Health Research Institution
• Principal Investigator: Xhorlina Marko, MD; Beaumont Dearborn Hospital
• Principal Investigator: Stephen Black, MD; St Thomas' Hospital (UK)

• PRS Account: Inari Medical
• Verification Date: May 2024