Clinical trial NCT00970619: DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT.
Official title: Ultrasound Accelerated Catheter-directed Thrombolysis for Primary Iliofemoral Deep Vein Thrombosis (IFDVT) Compared to Non-invasive Conventional Anticoagulant Therapy Alone: a Dutch Randomized Controlled Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Thrombosis of Deep Veins of Proximal Lower Extremity
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2009-09-02
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale: Iliofemoral deep venous thrombosis (IFDVT) is associated with significant post thrombotic morbidity. The presence of both obstruction and reflux significantly increases the chances for development of post-thrombotic syndrome (PTS). Early thrombolysis may reduce the incidence of PTS as compared to treatment with conventional anticoagulant medication alone. Improvement of the health related quality of life (HRQOL) has been reported after surgical clot removal. The investigators hypothesize that such improvements could also be reached after catheter-directed thrombolysis (CDT).

Objective: To assess whether CDT for the treatment of IFDVT can safely and effectively reduce post-thrombotic morbidity after one year. The secondary objective is to study whether CDT intervention has a positive effect on the HRQOL of patients with IFDVT and to assess late PTS.

Study design: Prospective, multicenter, single-blind, allocation concealed, randomized controlled trial Study population: All consecutive patients with IFDVT presenting at the emergency or outpatient departments of the participating centers. The thrombus should not be older than 14 days at randomization.

Intervention: After randomization patients will be allocated to either conservative anticoagulant treatment or to CDT combined with conservative anticoagulant treatment.

Main study parameters/endpoints: The primary efficacy outcome is the proportion of PTS at one year; a decline in PTS incidence from 25% to 8% is anticipated. The secondary outcome is the Health related Quality of life. The principal safety outcome is major bleeding during anticoagulant therapy. Bleeding as well as events of recurrent thrombosis will be monitored. Measurements of markers of coagulation and inflammation will be performed during follow-up. After CDT the patency of the venous system in the affected lower limb will be assessed as well as the percentage of clot lysis. The development of late PTS during follow-up will also be monitored.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For patients who are randomized to CDT a hospital stay for 24-96 hours is mandatory. All patients will undergo additional imaging by magnetic resonance venography and air phletysmography (if available) at baseline and after 12 months; blood will be taken at these visits. Clinical follow-up visits will be matching usual care at 3, 6, 12 months. Health-related quality of life (HRQOL) questionnaires will be filled out by all patients at baseline, 3, 6 and 12 months after the event; and once a year during the entire study duration. Further treatment will be in accordance with current guidelines for antithrombotic treatment. There may be an enhanced risk of bleeding in the thrombolysis group. The expected benefit is reduction of PTS from 25% to 8%, together with an improved quality of life.


Eligibility criteria: Inclusion Criteria:

* Objectively documented IFDVT
* Acute stage IFDVT, complaints less than 14 days
* Life expectancy longer than 6 months
* First thrombus in the affected limb

Exclusion Criteria:

* History of GI bleeding within 1 year
* History of cardiovascular accident /central nervous system disease within 1 year
* Severe hypertension (\>180/100 mmHg)
* Active malignancy
* Major surgery within 6 weeks
* Previous thrombosis of the affected limb (secondary thrombosis)
* Varicosities/venous insufficiency Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification C3 or higher
* Pregnancy
* Immobility (wheelchair dependent)
* Alanine aminotransferase (ALAT) \> 3 times normal range
* estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min

Primary outcomes:
measure: Post thrombotic syndrome (percentage of patients with PTS) one year following the acute thrombotic event.
timeFrame: one year
Secondary outcomes:
measure: The Health Related Quality of Life (HRQOL)
timeFrame: 5 years
measure: PTS during follow-up
timeFrame: 5 years
measure: Recurrent venous thrombo-embolisms (VTE): DVT/Pulmonary Embolism during follow-up
timeFrame: 5 years
measure: Clot lysis, patency and valve function
timeFrame: 5 years
measure: Measurements of markers of coagulation and inflammation
timeFrame: 5 years
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Amsterdam
country: Netherlands
facility: VuMC
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Drachten
country: Netherlands
facility: Nij Smellinghe
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
city: Eindhoven
country: Netherlands
facility: MMC Eindhoven
city: Geldrop
country: Netherlands
facility: St Anna Ziekenhuis
city: Heerlen
country: Netherlands
facility: Atrium MC Heerlen
city: Helmond
country: Netherlands
facility: Elkerliek Ziekenhuis
city: Nieuwegein
country: Netherlands
facility: St Antonius
city: Roermond
country: Netherlands
facility: Laurentius Roermond
city: Rotterdam
country: Netherlands
facility: Maasstad ziekenhuis
city: Venlo
country: Netherlands
facility: VieCuri
city: Weert
country: Netherlands
facility: Sint Jans Gasthuis
city: Zwolle
country: Netherlands
facility: Isala klinieken
Study officials:
affiliation: Maastricht University Medical Centre
name: Hugo ten Cate, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arnoldussen CWKP, Notten P, Brans R, Vroegindeweij D, Tick LW, van de Poel MHW, Wikkeling ORM, Vleming LJ, Koster A, Jie KG, Jacobs EMG, Planken N, Wittens CHA, Ten Cate H, Wildberger JE, Ten Cate-Hoek AJ. Clinical impact of assessing thrombus age using magnetic resonance venography prior to catheter-directed thrombolysis. Eur Radiol. 2022 Jul;32(7):4555-4564. doi: 10.1007/s00330-022-08599-5. Epub 2022 Mar 28.
citation: Notten P, de Smet AAEA, Tick LW, van de Poel MHW, Wikkeling ORM, Vleming LJ, Koster A, Jie KG, Jacobs EMG, Ebben HP, Coppens M, Ten Cate H, Wittens CHA, Ten Cate-Hoek AJ. CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis on Preventing Post-Thrombotic Syndrome) Trial: Long-Term Follow-Up Results. J Am Heart Assoc. 2021 Jun;10(11):e018973. doi: 10.1161/JAHA.120.018973. Epub 2021 May 25.
citation: Notten P, Arnoldussen CWKP, Brans R, de Smet AAEA, Tick LW, van de Poel MHW, Wikkeling ORM, Vleming LJ, Koster A, Jie KG, Jacobs EMG, Ebben HP, Planken N, Ten Cate H, Wittens CHA, Ten Cate-Hoek AJ. Association of Successful Ultrasound-Accelerated Catheter-Directed Thrombolysis with Postthrombotic Syndrome: A Post Hoc Analysis of the CAVA Trial. Thromb Haemost. 2020 Aug;120(8):1188-1199. doi: 10.1055/s-0040-1713171. Epub 2020 Jun 30.
citation: Notten P, Ten Cate-Hoek AJ, Arnoldussen CWKP, Strijkers RHW, de Smet AAEA, Tick LW, van de Poel MHW, Wikkeling ORM, Vleming LJ, Koster A, Jie KG, Jacobs EMG, Ebben HP, Coppens M, Toonder I, Ten Cate H, Wittens CHA. Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial. Lancet Haematol. 2020 Jan;7(1):e40-e49. doi: 10.1016/S2352-3026(19)30209-1. Epub 2019 Nov 27.