Endovascular Therapy in Patients With Acute Deep Vein Thrombosis

Completed

• Conditions: Acute Deep Venous Thrombosis
• Interventions: Device: Local catheter directed thrombolysis alone; Device: Mechanical / pharmacomechanical thrombectomy plus local catheter directed thrombolysis

• Registration Number: NCT05827120
• Lead Sponsor: National Institute of Cardiovascular Diseases, Slovakia

Brief Summary

Despite optimal anticoagulation therapy of patients with proximal deep vein thrombosis (DVT), there is still high number of patients suffering from post-thrombotic syndrome (PTS) due to the chronic venous occlusion, suboptimal collateralization, and venous valvular dysfunction. Last two decades endovascular catheter-based treatment modalities have been tested and used in an attempt to reduce incidence and symptoms of PTS in selected patients.

Especially, patients with extensive iliofemoral DVT have an increased risk of PTS. In an effort to accelerate thrombus dissolution or thrombus extraction, the endovascular removal of acute venous thrombus has been introduced as therapeutic option in patients with extensive iliofemoral DVT.

Randomized trials of catheter-based strategies for thrombus removal have documented improved vein patency, preserved valves function, and reduced post-thrombotic syndrome.

The aim of our study is to evaluate the safety and efficacy of different types of endovascular methods of treatment followed by anticoagulation therapy in patients with acute extensive DVT. Retrospective multicentre analysis of app 100 patients scheduled for endovascular treatment of extensive DVT. The results of mechanical/pharmacomechanical thrombectomy followed by local catheter directed thrombolysis (CDT), will be compared with CDT alone, or with ultrasound-accelerated thrombolysis. The 24-month incidence of PTS assessed by Villalta scoring system, major bleeding complications, the rate of venous recanalization, recurrence of DVT, and other end-points will be evaluated.

Detailed Description

Aim: The aim of the study is to evaluate the long-term incidence of PTS in patients treated by different endovascular methods and protocols in combination with anticoagulation medication in patients with acute extensive DVT.

Hypothesis: Mechanical / pharmacomechanical thrombectomy (PMT) following by CDT and further anticoagulation therapy is safe and effective mode of acute DVT treatment with reduction of PTS after 24 months in comparison with historical data and with other modes of endovascular therapy.

Methods: Retrospective multicentre analysis of patients scheduled to interventional endovenous treatment of extensive DVT.

The major end-point:

1. The development of PTS during the 24-month follow-up period

The minor end-points:

1. The occurrence of major bleeding and live-threatening bleeding episodes

2. The development of PTS during the 6-month and 12-month follow-up period

3. The rate of venous recanalization after intervention assessed by ultrasound

4. The occurrence of pulmonary embolism

5. Recurrence of DVT

6. Mortality, myocardial infarction, stroke during follow-up

The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system.

Patients suitable for endovascular therapy and for enrolment into study:

* first episode of acute iliofemoral DVT

* duration of symptoms \<14 days

* symptomatic patients with no or limited response to initial anticoagulation therapy in terms of symptomatology and signs of recanalization

* low bleeding risk

* good functional capacity and life expectancy

Endovascular procedures retrospectively analysed:

* Catheter directed thrombolysis (CDT): dedicated infusion catheter with side holes is placed across the acute thrombus, and slow, continuous infusion (through the catheter, or both through the catheter and sheath) of a chemical thrombolysis agent is initiated (alteplase 1mg per hour simultaneously with unfractionated heparine (UFH) in anticoagulation dosage); activated partial thromboplastin time (APTT), fibrinogen (Fbg), and blood count must be controlled;

* Mechanical thrombectomy: mechanical aspiration of fresh thrombus; mostly followed by CDT;

* Pharmacomechanical thrombectomy (PMT): combination of some form of mechanical disruption of the thrombus in conjunction with chemical lysis. There is evidence that PMT quickens thrombolysis compared with CDT alone. Dedicated devices combining chemical thrombolysis via power-pulse fluid plus plasminogen activator thrombus penetration, with rheolytic fluid-based disruption of thrombus and catheter-based aspiration thrombectomy.

* Ultrasound-accelerated thrombolysis combines chemical CDT with low-power high-frequency ultrasound application to the proprietary infusion catheter/wire combination, with the ultrasonic vibration purported to hasten thrombus disruption; the addition of ultrasound during lytic infusion increases the surface area of the fibrin, thereby permitting more efficient binding of the plasminogen activator to the fibrin-bound plasminogen

* Stenting of residual thrombotic lesions, and stenting of common iliac vein compression in the presence of May-Thurner syndrome;

Peri-procedure and post-procedure care retrospectively analysed:

* continuous in-hospital monitoring to minimize CDT-related complications;

* APTT, Fbg concentration, and blood count are monitored;

* Anticoagulation after endovascular procedure as standard regimen, if no contraindications, mostly during the 6-month time period; longer anticoagulation regimen is at discretion of treated centre and physician;

* after venous stenting may be consider clopidogrel along with anticoagulation therapy for 1 month (not proven); Ultrasound evaluation during follow-up (data from documentation)

* recanalization - no residual thrombosis

* recanalization \>50%

* recanalization \<50%

* minimal US signs of recanalization/no recanalization Post-thrombotic syndrome: clinical evaluation and/or Villalta score

* No PTS: Villalta \<5 points

* Mild: 5-9 points

* Moderate: 10-14 points

* Severe PTS: ≥15 points/venous ulcer

Study Timeline

• Study Start: 2021-03-23
• Primary Completion: 2023-02-24
• Study Completion: 2023-02-24
• Status Verified: 2023-04
• Study First Submitted: 2023-04-06
• Study First Submitted QC: 2023-04-21
• Last Update Submitted: 2023-04-23
• Study First Posted: 2023-04-24
• Last Update Posted: 2023-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• first episode of acute iliofemoral DVT
• duration of symptoms <14 days
• symptomatic patients with no or limited response to initial anticoagulation therapy in terms of symptomatology and signs of recanalization
• low bleeding risk
• good functional capacity and life expectancy

Exclusion Criteria

• • presence of malignity (2 centers out of 3)
• pregnancy
• haemorrhagic diathesis / high risk of bleeding
• negative prognosis of survival
• renal / hepatic failure
• chronic course of DVT

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Local catheter directed thrombolysis alone group	Local catheter directed thrombolysis alone	Local catheter directed thrombolysis alone group - patients treated by dedicated catheter for local thrombolysis with side holes placed across the acute thrombus - continuous infusion of alteplase 1mg per hour simultaneously with unfractionated heparine in anticoagulation dosage. Without mechanical or pharmaco-mechanical thrombectomy. Procedure followed by anticoagulation therapy.
Thrombectomy plus local thrombolysis group	Mechanical / pharmacomechanical thrombectomy plus local catheter directed thrombolysis	Thrombectomy plus local thrombolysis group - patients treated by mechanical thrombectomy mostly followed by catheter directed thrombolysis (CDT), or by pharmaco-mechanical thrombectomy (PMT) - combination of some form of mechanical disruption of the thrombus in conjunction with chemical lysis. Thrombolysis by alteplase 1mg/hour. Procedure followed by anticoagulation therapy.

Primary Outcome Measures

Name	Time	Method
Post-thrombotic syndrome	24-month follow-up period	The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system (0-33), higher scores mean a worse outcome.

Secondary Outcome Measures

Name	Time	Method
The rate of venous recanalization after intervention	early - in-hospital (up to day 7), 6-month	assessed by ultrasound
The development of PTS during the 6-month and 12-month follow-up period	6-month and 12-month follow-up period	The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system (0-33), higher scores mean a worse outcome.
Mortality, MI, stroke during follow-up	In-hospital (up to day 7), 12-month, 24-month follow-up	history assessment
The occurrence of pulmonary embolism	early - in-hospital (up to day 7), 12-month, 24-month follow-up	clinical evaluation
Recurrence of DVT	12-month, 24-month follow-up	clinical and ultrasound evaluation
The occurrence of major bleeding and live-threatening bleeding episodes	periprocedural, in-hospital (up to day 7), 24 months	clinical and laboratory evaluation of bleeding

Trial Locations

Locations (3)

Central Slovakia Institute of Cardiovascular Diseases in Banská Bystrica; 🇸🇰 Banská Bystrica, Slovakia

National Institute of Cardiovascular Diseases, Slovakia; 🇸🇰 Bratislava, Slovakia

East Slovakia Institute of Cardiovascular Diseases in Košice; 🇸🇰 Košice, Slovakia