Clinical trial NCT00251771: Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis
Official title: Catheter-directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis, an Open Randomized, Controlled, Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Deep Vein Thrombosis
Keywords: Thrombolytic therapy
Postphlebitic syndrome
Venous thrombosis
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Ostfold Hospital Trust
First posted: 2005-11-10
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Deep vein thrombosis (DVT) is a severe disease, and conventional treatment with low molecular weight heparin (LMWH) and warfarin is associated with some degree of long-term sequelae, i.e. post-thrombotic syndrome (PTS). Catheter-directed thrombolytic (CDT) therapy has been introduced worldwide the last two decades. Reports have suggested a beneficial effect of this costly treatment, but there are no randomized clinical trials documenting its short- and long-term efficacy and safety. This multi-center study will randomize patients with acute iliofemoral vein thrombosis to either conventional treatment or CDT in addition to conventional treatment. Main outcome parameters are patency rates at 6 months and prevalence of PTS at 24 months. The main short-term hypothesis is that CDT of first-time acute DVT will increase patency of the affected segments after 6 months from \<50% to \>80%. The main long-term hypothesis is that CDT will improve long-term functional outcome, i.e. risk of PTS after 2 years from \>25% to \<10%.


Eligibility criteria: Inclusion Criteria:

* Onset of symptoms \<21 days
* Objectively verified DVT of the femoral or common iliac veins or the combined iliofemoral segment
* Informed consent

Exclusion Criteria:

* Anticoagulant therapy prior to trial entry \>7 days
* Contraindications to thrombolytic therapy
* Indications for thrombolytic therapy, i.e. phlegmasia coerulea dolens or vena cava thrombosis
* Severe anemia, hemoglobin (hgb)\<8 g/dl
* Thrombocytopenia, platelets \<80x10\^9/l
* Severe renal failure, creatinine clearance \<30ml/min
* Severe hypertension, systolic (syst) blood pressure (BP)\>160 mmHg or diastolic (diast) BP \>100 mmHg pregnancy
* Less than 14 days post-surgery or post-trauma
* History of subarachnoidal or intracerebral bleeding
* Disease with life expectancy \<24 months
* Drug abuse or mental disease that may interfere with treatment and follow-up
* Former ipsilateral proximal DVT
* Chemotherapy or advanced malignant disease

Primary outcomes:
measure: Patency after 6 months
timeFrame: 6 months
measure: Post-thrombotic syndrome after 2 years (yrs)
timeFrame: 2 years
Secondary outcomes:
measure: Frequency of clinically relevant bleeding complications
timeFrame: 1 year
measure: Effects on quality of life
timeFrame: 2 and 5 years
measure: Cost-effectiveness of treatment
timeFrame: 2 years
measure: Procedural success of CDT
timeFrame: 1 week
measure: Patency at 2 years
timeFrame: 2 years
measure: PTS at 6, 12, 36, 48 and 60 months
timeFrame: 6, 12, 36, 48 and 60 months
measure: Relation between PTS and patency
timeFrame: 2 years
measure: Prevalence of vein anomalies
timeFrame: 6 months
measure: Prevalence of underlying thrombophilia
timeFrame: 1 year
measure: Frequency of recurrent venous thrombotic events (VTE)
timeFrame: 0.5, 2 and 5 years
measure: Markers of importance for recurrent thrombosis
timeFrame: 0.5, 2 and 5 years
measure: Markers of importance for successful thrombolysis
timeFrame: 2 years
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Ullevaal University Hospital
Study officials:
affiliation: Ullevaal University Hospital
name: Per Morten Sandset, MD
role: STUDY_DIRECTOR
References:
citation: Enden T, Klow NE, Sandset PM. [Catheter-directed thrombolysis in acute deep venous thrombosis]. Tidsskr Nor Laegeforen. 2006 Jun 22;126(13):1765. No abstract available. Norwegian.
citation: Enden T, Sandvik L, Klow NE, Hafsahl G, Holme PA, Holmen LO, Ghanima W, Njaastad AM, Sandbaek G, Slagsvold CE, Sandset PM. Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis--the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). Am Heart J. 2007 Nov;154(5):808-14. doi: 10.1016/j.ahj.2007.07.010. Epub 2007 Sep 6.
citation: Enden T, Garratt AM, Klow NE, Sandset PM. Assessing burden of illness following acute deep vein thrombosis: data quality, reliability and validity of the Norwegian version of VEINES-QOL/Sym, a disease-specific questionnaire. Scand J Caring Sci. 2009 Jun;23(2):369-74. doi: 10.1111/j.1471-6712.2008.00618.x. Epub 2008 Nov 12.
citation: Enden T, Sandset PM, Klow NE. Evidence-based practice for patients with severe venous thrombosis. Tidsskr Nor Laegeforen. 2012 May 29;132(10):1215-6. doi: 10.4045/tidsskr.12.0474. No abstract available. English, Norwegian.
citation: Enden T, Klow NE, Sandvik L, Slagsvold CE, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM; CaVenT study group. Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency. J Thromb Haemost. 2009 Aug;7(8):1268-75. doi: 10.1111/j.1538-7836.2009.03464.x. Epub 2009 Apr 30.
citation: Enden T, Haig Y, Klow NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012 Jan 7;379(9810):31-8. doi: 10.1016/S0140-6736(11)61753-4. Epub 2011 Dec 13.
citation: Haig Y, Enden T, Slagsvold CE, Sandvik L, Sandset PM, Klow NE. Determinants of early and long-term efficacy of catheter-directed thrombolysis in proximal deep vein thrombosis. J Vasc Interv Radiol. 2013 Jan;24(1):17-24; quiz 26. doi: 10.1016/j.jvir.2012.09.023. Epub 2012 Nov 22.
citation: Enden T, Resch S, White C, Wik HS, Klow NE, Sandset PM. Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis. J Thromb Haemost. 2013 Jun;11(6):1032-42. doi: 10.1111/jth.12184.
citation: Enden T, Wik HS, Kvam AK, Haig Y, Klow NE, Sandset PM. Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study. BMJ Open. 2013 Aug 29;3(8):e002984. doi: 10.1136/bmjopen-2013-002984.
citation: Enden T, Klow NE, Sandset PM. Symptom burden and job absenteeism after treatment with additional catheter-directed thrombolysis for deep vein thrombosis. Patient Relat Outcome Meas. 2013 Sep 16;4:55-9. doi: 10.2147/PROM.S47233. eCollection 2013.
citation: Broderick C, Watson L, Armon MP. Thrombolytic strategies versus standard anticoagulation for acute deep vein thrombosis of the lower limb. Cochrane Database Syst Rev. 2021 Jan 19;1(1):CD002783. doi: 10.1002/14651858.CD002783.pub5.
citation: Haig Y, Enden T, Grotta O, Klow NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016 Feb;3(2):e64-71. doi: 10.1016/S2352-3026(15)00248-3. Epub 2016 Jan 6.