Clinical trial NCT05701917: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Venous Thromboembolism
Deep Venous Thrombosis
Post-Thrombotic Syndrome
Keywords: Venous Thromboembolism
Deep Venous Thrombosis
Post-Thrombotic Syndrome
Anticoagulation
Percutaneous Mechanical Thrombectomy
Lead sponsor: Inari Medical
Sponsor class: INDUSTRY
First posted: 2023-01-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. Approximately 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).

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

Primary outcomes:
measure: Composite clinical endpoint constructed as a win ratio, a hierarchy of the following:
timeFrame: 180 Days (+-14 Days)
Secondary outcomes:
measure: Composite clinical endpoint constructed as a win ratio, a hierarchy of the following:
timeFrame: 10 Days (+- 3 Days)
measure: Assessment of PTS Severity:
timeFrame: 180 Days (+-14 Days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: Tucson
country: United States
facility: Pima Heart and Vascular
state: Arizona
city: Orange
country: United States
facility: UCI Medical Center
state: California
city: Orange
country: United States
facility: Vascular and Interventional Specialists of Orange County
state: California
city: Denver
country: United States
facility: University Of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institution
state: District of Columbia
city: Bradenton
country: United States
facility: Manatee Memorial Hospital
state: Florida
city: Lakeland
country: United States
facility: Lakeland Vascular Institute
state: Florida
city: Largo
country: United States
facility: HCA Florida Largo Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: BayCare Health System
state: Florida
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Munster
country: United States
facility: Community Healthcare System
state: Indiana
city: Edgewood
country: United States
facility: St. Elizabeth Edgewood
state: Kentucky
city: Bay City
country: United States
facility: McLaren Healthcare
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Bay Shore
country: United States
facility: Northwell Health
state: New York
city: Brooklyn
country: United States
facility: NYP-Brooklyn Methodist
state: New York
city: Buffalo
country: United States
facility: SUNY, The University at Buffalo
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Health
state: North Carolina
city: Cincinnati
country: United States
facility: Mercy Health - The Heart Institute
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: Saint Francis Hospital
state: Oklahoma
city: Erie
country: United States
facility: Allegheny St. Vincent Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Health Research Network
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: West Columbia
country: United States
facility: Lexington Medical Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Clements University Hospital (UTSW)
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Med Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Würtemberg
city: Frankfurt
country: Germany
facility: MVZ CCB Frankfurt und Main-Taunus GbR
state: Hessen
city: Arnsberg
country: Germany
facility: Klinikum Hochsauerland GmbH
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universität Leipzig
state: Sachsen
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bern
country: Switzerland
facility: Inselspital, Universitätsspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: London
country: United Kingdom
facility: GSST London/St Thomas
city: London
country: United Kingdom
facility: Imperial College
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital Newcastle upon Tyne
city: Oxford
country: United Kingdom
facility: Oxford - John Radcliffe
Study officials:
affiliation: MedStar Health Research Institution
name: Steven Abramowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health
name: Xhorlina Marko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Thomas' Hospital (UK)
name: Stephen Black, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abramowitz SD, Marko X, D'Souza D, Noor S, Pereira K, Silver MJ, Rosenberg SP, Markovitz CD, Tu T, Weinberg I, Black S. Rationale and design of the DEFIANCE study: A randomized controlled trial of mechanical thrombectomy versus anticoagulation alone for iliofemoral deep vein thrombosis. Am Heart J. 2025 Mar;281:92-102. doi: 10.1016/j.ahj.2024.10.016. Epub 2024 Nov 3.