Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis-the CaVenT Study: Rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771)

doi:10.1016/j.ahj.2007.07.010

American Heart Journal

Volume 154, Issue 5, November 2007, Pages 808-814

https://doi.org/10.1016/j.ahj.2007.07.010 Get rights and content

Background

The conventional treatment of acute deep vein thrombosis (DVT) is anticoagulation and compression therapy, as recommended in the international guidelines. Anticoagulation prevents recurrent venous thrombosis, pulmonary embolism, and death. Compression therapy reduces the risk of developing long-term sequelae, that is, postthrombotic syndrome (PTS). Evaluation of systemic thrombolysis has shown effective thrombolysis and a likely reduction in PTS but at the cost of increased risk of bleeding complications. Catheter-directed thrombolysis (CDT) was introduced for rapid removal of thrombi and salvage of venous valves with less systemic thrombolytic effect, and is being offered to selected patients with iliofemoral DVT to prevent development of PTS. Case series have shown technical and thrombolytic success; however, no randomized studies have evaluated the long-term clinical effects of venous CDT. The aim of the CaVenT study is to investigate the role of adjunctive CDT by evaluating its clinical efficacy and safety compared with conventional treatment alone in patients with acute iliofemoral DVT.

Methods

The CaVenT study is an open, randomized, controlled, clinical trial. We plan to include 200 patients who will receive either CDT, in addition to conventional treatment, or conventional treatment alone. The primary outcome measures are patency at 6 months and prevalence of PTS at 2 years.

Conclusion

Implementation of the CaVenT study will be a contribution toward evidence-based medicine in the treatment of acute proximal DVT of the leg. Any documentation of improved functional outcome will have a significant impact on clinical practice for this patient group and may lead to a modification of existing international guidelines.

Section snippets

Study objectives

The primary objectives of the CaVenT study is to investigate whether adjunctive CDT for first-time acute iliofemoral DVT increases patency rate at 6 months and/or reduces the incidence of PTS at 2 years. Our secondary objectives are to describe frequency of clinically relevant bleeding related to the procedure, effects on health-related quality of life (QOL), cost-effectiveness, procedural success, markers of importance for successful thrombolysis, patency at 2 years, PTS at 6 and 60 months,

Sample size

Quite diverse prevalence of PTS has been reported. In a recent meta-analysis including 2 studies evaluating thrombolysis versus AC for acute DVT, PTS was reported in 65% (26/49) of the controls and 48% (29/61) in the intervention group.⁷ A review of 4 studies evaluating the systematic use of elastic compression stockings showed a reduction in prevalence of PTS from 54% to 25%.²⁰ Accordingly, we assume that the prevalence of PTS after 2 years will be at least 25% in those allocated conventional

Trial organization and funding

The study is an investigator-initiated study running independently of the pharmaceutical industry, and it is a major collaborative effort among most hospitals of the Southern and Eastern Norway Regional Health Authority (Helse Sør and Øst RHF). The study is financially supported by grants from the Eastern Norway Health Authority (doctoral fellow, Helse Øst grant 2005-090) and the Norwegian Research Council (project no. ES376301). Approvals have been obtained by Regional Ethics Committee East

Discussion

To our knowledge, the CaVenT study is the first implemented randomized controlled trial designed to evaluate the long-term clinically relevant efficacy of adjunctive CDT in patients with iliofemoral DVT, and our study protocol is in line with recently published reporting standards.²³ Current status of the trial (86 patients recruited during the first 17 months) supports our appraisal that it is possible to obtain the necessary number of patients (n = 200) within a reasonable period.

The inherent

Conclusion

Clinical experience with CDT over the last years has lead to the development of a safe and improved procedure. However, venous CDT is still regarded as an experimental adjunctive therapy. Implementation of the CaVenT study will be an important contribution toward evidence-based medicine in the treatment of acute proximal DVT of the leg. Any documentation of improved functional outcome will most likely have a significant impact on clinical practice for this patient group and may lead to a

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Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials
2022, European Journal of Vascular and Endovascular Surgery
Citation Excerpt :
These articles were assessed for eligibility and 755 articles were excluded as they were deemed not relevant to the review. Full texts were obtained for the remaining 43 articles and further evaluation narrowed the research results to seven studies (16 articles).2,12–14,27–37 These were incorporated in this study.
To investigate the outcomes of treatment strategies for proximal and iliofemoral deep vein thrombosis (DVT).
Randomised controlled trials (RCTs) investigating outcomes of catheter directed thrombolysis (CDT), ultrasound assisted CDT (USCDT), percutaneous aspiration thrombectomy (PAT), and best medical therapy (BMT) for proximal DVT from 2000 onwards were considered. MEDLINE, EMBASE, and CINAHL were searched using the Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence. The primary outcome was the rate of post-thrombotic syndrome (PTS), which was defined using the Villalta scoring system (score of ≥5). Secondary outcomes included vessel patency, recurrence, bleeding, and mortality. The network of evidence was summarised using network plots, and random effects network meta-analyses were performed. The certainty of evidence was assessed using the Certainty In Network Meta-Analysis (CINeMA) approach.
Seven RCTs meeting the inclusion criteria were identified. There were direct comparisons between medical therapy, CDT, and USCDT across outcomes, except for patency. There were no direct comparisons between medical therapy and PAT (except for patency), and USCDT and PAT. There was no significant difference observed in PTS between the treatment modalities for proximal and iliofemoral DVT (low certainty). There was a significant difference in patency rates between medical therapy and USCDT (odds ratio [OR] 9.46, 95% confidence interval [CI] 3.05 – 29.35; low certainty) and CDT (OR 2.03, 95% CI 1.46 – 2.80; low certainty) in favour of USCDT and CDT, respectively, for proximal DVT. USCDT significantly improved patency rates compared with CDT (OR 4.67, 95% CI 1.58 – 13.81; very low certainty) for proximal DVT. There was no significant difference in DVT recurrence, bleeding, or mortality between treatment groups for proximal and iliofemoral DVT (low to moderate certainty for most comparisons).
USCDT may improve patency rates compared with BMT and the other interventional treatment modalities used for the management of proximal DVT. However, no treatment modality showed superiority with regard to a reduction in PTS, and overall, the quality of available evidence is poor.
Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report
2021, Chest
This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.
We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.
The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.
New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.
Limitations of the Villalta scale in diagnosing post-thrombotic syndrome
2019, Thrombosis Research
Citation Excerpt :
The present study aimed to examine the accuracy of the Villalta scale using four predefined clinical criteria in line with clinical practice as a reference standard in patients with a history of upper femoral and/or iliac DVT. In 2017 we invited the 170 patients still alive who were included in 2006–09 for a randomized clinical study that compared additional catheter-directed thrombolysis (CDT) for high proximal DVT to conventional anticoagulant treatment, the catheter-directed venous thrombolysis (CaVenT)study [12,22,23] to participate in a one time visit, cross-sectional follow-up study. The southeastern Norway Regional Committee for Medical and Health Research Ethics (REK) approved the study (no. 2015/1567), and written informed consent was obtained from all participants.
The Villalta scale is currently the recommended tool for diagnosing post-thrombotic syndrome (PTS) in clinical studies, but there is concern that the sensitivity and specificity of the scale might be low. We aimed to evaluate the diagnostic accuracy of the Villata scale using criteria in line with clinical practice as a reference.
We invited patients with a history of proximal DVT during 2006–09 to participate in a cross-sectional follow-up study of long-term complications after DVT. PTS was diagnosed by the Villalta scale, and by the following four mandatory and predefined clinical criteria used as a reference for PTS: 1. Objectively verified DVT; 2. chronic complaints (>1 month) in the DVT leg; 3. complaints appeared after the DVT; and 4. an alternative diagnosis was unlikely.
We included 88 of 170 eligible patients (52%). With our clinical criteria as a reference the sensitivity and specificity of the Villalta scale for diagnosing PTS were 75% (95% CI 60–87%) and 66% (95% CI 50–80%), respectively. Fifteen patients were diagnosed with PTS by the Villalta scale only. These patients more often experienced pain or had comorbidity that could explain their leg symptoms and signs. Eleven patients diagnosed with PTS by the clinical criteria only, had more fluctuating heaviness and edema.
Our findings indicate that the diagnostic accuracy of the Villalta scale has limitations. Incorporating chronicity, whether the leg problems appeared following the DVT, fluctuations of heaviness and edema, and comorbidity in PTS assessment may improve the diagnostic accuracy.
Posterior tibial vein approach to catheter-directed thrombolysis for iliofemoral deep venous thrombosis
2019, Journal of Vascular Surgery: Venous and Lymphatic Disorders
Deep venous thrombosis (DVT) remains a significant cause of morbidity in the American population. Catheter-directed thrombolysis for acute iliofemoral DVT is an effective therapy not only to restore venous patency but also to reduce the development of post-thrombotic syndrome (PTS), especially in patients with extensive thrombosis involving the iliac and femoral venous segments. We hypothesized that delivery of thrombolytics through an access site in a vein distal to the segments containing thrombus would provide the greatest short- and long-term therapeutic clinical benefit with similar safety and efficacy.
All patients treated at a single institution between 2009 and 2016 undergoing mechanical and chemical thrombolysis for iliofemoral DVT were retrospectively reviewed. Patients were divided into groups by access site, including contralateral and ipsilateral femoral vein, popliteal vein, and posterior tibial vein (PTV). Preoperative demographics, intraoperative data, and postoperative outpatient charts were analyzed. Primary end points included evidence of incompetence after the procedure by duplex ultrasound assessment and development of complications of PTS as defined by the Villalta scale.
Fifty-eight patients underwent mechanical and chemical thrombolysis, and 51 patients met the inclusion criteria. Thrombolysis access was through PTV (n = 27), popliteal vein (n = 20), or femoral vein (n = 4). More patients were female (55%), and the mean age was 57 years. Forty patients had unilateral DVT, whereas 11 patients had bilateral involvement. After lysis, 44 patients underwent percutaneous venous angioplasty and 11 patients underwent venous stenting in the acute setting. Although not statistically significant, mean operative times were slightly longer in the posterior tibial approach (156.7 minutes vs 130.6 minutes; P = .08), and mean fluoroscopy time was higher in the posterior tibial group (18.1 minutes vs 14.3 minutes; P = .17). Overall 90-day morbidity was 9.8%, and no deaths were recorded. Patency of the deep venous system was similar between the posterior tibial and the popliteal or femoral approach (95% vs 88%; P = .29); 21.6% developed symptoms of PTS. There was no difference for development of PTS between posterior tibial and popliteal or femoral approaches (22% vs 20.8%; P = .52). There was no difference in development of chronic nonocclusive DVT (37% vs 35%; P = .61). Median follow-up was 8.7 months (range, 0.4-58.9 months).
The PTV approach to catheter-directed thrombolysis is a safe and sensible option for the treatment of iliofemoral and femoropopliteal DVT. A larger cohort will be necessary to demonstrate superiority of tibial vein access in the treatment of iliofemoral DVT with popliteal involvement.
A high Gas6 level in plasma predicts venous thromboembolism recurrence, major bleeding and mortality in the elderly: a prospective multicenter cohort study
2019, Journal of Thrombosis and Haemostasis
Background
Growth arrest‐specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging.
To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly.
Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA.
Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C‐statistic, 0.56; 95% confidence interval [CI] 0.51–0.62), major bleeding (0.60, 95% CI 0.55–0.65) and mortality (0.69, 95% CI 0.65–0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54–0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively.
In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation.
Risk of Acute Kidney Injury after Percutaneous Pharmacomechanical Thrombectomy Using AngioJet in Venous and Arterial Thrombosis
2017, Annals of Vascular Surgery
Percutaneous mechanical thrombectomy is commonly used to treat acute thrombotic syndromes. AngioJet (AJ) forcibly sprays fibrinolytics to fragment and aspirate thrombus. It is known to cause hemolysis and gross hematuria, yet potential consequences to renal function after AJ remain unstudied. We sought to determine the risk of acute kidney injury (AKI) after AJ when compared with other lysis techniques.
We retrospectively reviewed patients treated with thrombolysis over 5 years. We identified those treated with AJ or catheter-directed thrombolysis (CDT). Demographics, indications, procedures, and laboratory values within 3 days were recorded. AKI was defined as an increase >25% above the baseline creatinine within 72 hr of the procedure. IN total, 102 patients (52 AJ, 50 CDT) had no statistical difference in mean age (50 and 51), indication (arterial thrombosis 65% and 88%), or baseline creatinine (0.9 and 1.0 mg/dL), respectively. AKI occurred in 15 (29%) patients treated with AJ versus 4 (8%) of CDT (P = 0.007). Similar numbers of AJ and CDT patients underwent additional open surgical procedures (21% and 30%, respectively, P = not significant). Multivariable analysis demonstrated that the odds of AKI were only increased by AJ (odds ratio [OR] 8.2, 95% confidence interval [CI] 1.98–34.17, P = 0.004), open surgery (OR 5.4, 95% CI 1.43–20.17, P = 0.013), or a >10% drop in hematocrit (OR 4.0, 95% CI 1.15–14.25, P = 0.03).
In our observational study, AJ is an independent risk factor for AKI. Concomitant open surgery and drop in hematocrit also raise the odds of AKI. Renal injury after AJ is under-reported in the literature, and may be related to hemolysis from the device.

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Trial DesignCatheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis-the CaVenT Study: Rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771)

Background

Methods

Conclusion

Section snippets

Study objectives

Sample size

Trial organization and funding

Discussion

Conclusion

Lancet

Tech Vasc Interv Radiol

J Vasc Interv Radiol

Eur J Vasc Endovasc Surg

Eur J Vasc Endovasc Surg

J Vasc Interv Radiol

J Vasc Surg

Health Policy

J Vasc Interv Radiol

Eur J Vasc Endovasc Surg

J Thromb Haemost

The Lancet

The epidemiology of venous thromboembolism

Circulation

Trial Design
Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis-the CaVenT Study: Rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771)