Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black
{"title":"DEFIANCE 研究的原理和设计:机械血栓切除术与单纯抗凝治疗髂股深静脉血栓的随机对照试验。","authors":"Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black","doi":"10.1016/j.ahj.2024.10.016","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.</p><p><strong>Methods: </strong>The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism.</p><p><strong>Conclusions: </strong>DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity.</p><p><strong>Trial registration: </strong>DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rationale and Design of the DEFIANCE Study: A Randomized Controlled Trial of Mechanical Thrombectomy Versus Anticoagulation Alone for Iliofemoral Deep Vein Thrombosis.\",\"authors\":\"Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black\",\"doi\":\"10.1016/j.ahj.2024.10.016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.</p><p><strong>Methods: </strong>The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism.</p><p><strong>Conclusions: </strong>DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity.</p><p><strong>Trial registration: </strong>DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1.</p>\",\"PeriodicalId\":7868,\"journal\":{\"name\":\"American heart journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American heart journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ahj.2024.10.016\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American heart journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ahj.2024.10.016","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Rationale and Design of the DEFIANCE Study: A Randomized Controlled Trial of Mechanical Thrombectomy Versus Anticoagulation Alone for Iliofemoral Deep Vein Thrombosis.
Background: Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.
Methods: The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism.
Conclusions: DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity.
Trial registration: DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1.
期刊介绍:
The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.