Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: Inclusion Criteria:

* All outpatients with an acute, symptomatic, distal DVT will be included in the study, provided they correspond to the following diagnostic and exclusion criteria, and they have signed an informed consent form.

Exclusion Criteria:

* Age less than 18 years
* Previously objectively diagnosed DVT or PE
* Distal DVT involving the tibioperoneal trunk (i.e. calf trifurcation)
* Clinically suspected pulmonary embolism
* Active cancer, receiving cancer treatment or cancer considered cured for \<6 months
* Ipsilateral or contralateral proximal DVT
* Indication for long-term anticoagulation (e.g. atrial fibrillation, mechanical heart valve...)
* Pregnancy
* Thrombocytopenia (platelet count \< 100 g/l)
* Impaired renal function (serum creatinine \> 180 micromol/l or clearance to creatinine less than 30 ml/min)
* Known hypersensitivity to heparin
* Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (gastric ulcer, cerebral malignant disease...)
* Treatment with daily NSAIDs (aspirin ≤160 mg/day permitted)
* Body weight \>115 kg or \<40 kg
* Treatment with therapeutic doses of anticoagulants for \>2 days, corresponding to: 2 injections of LMWH if once daily therapeutic LMWH used; 3 injections of LMWH if twice-daily therapeutic LMWH used; 1 dose of oral vitamin K antagonist (e.g. warfarin)
* Ongoing requirement for prophylactic dose thromboprophylaxis (e.g. acute post-op patient receiving thromboprophylaxis)
* Enrolled in another clinical trial within previous 30 days
* Inability or refusal to provide informed consent
B: 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
C: Inclusion Criteria:

* Female and male patients
* Patients \>= 18 years
* Patiebts with diagnosis of acute DVT and who have an indication for anticoagulation therapy for at least 12 weeks, who are willing to participate in this study and are available for follow-up

Exclusion Criteria:

* Exclusion criteria must be read in conjunction with the local product information.
D: Inclusion Criteria:

* Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein.

Exclusion Criteria:

* Age less than 16 years or greater than 75 years.
* Symptom duration \> 14 days for the DVT episode in the index leg (i.e., non-acute DVT).
* In the index leg: established PTS, or previous symptomatic DVT within the last 2 years.
* In the contralateral (non-index) leg: symptomatic acute DVT a) involving the iliac and/or common femoral vein; or b) for which thrombolysis is planned as part of the initial therapy.
* Limb-threatening circulatory compromise.
* Pulmonary embolism with hemodynamic compromise (i.e., hypotension).
* Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.
* Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
* Hemoglobin \< 9.0 mg/dl, INR \> 1.6 before warfarin was started, or platelets \< 100,000/ml.
* Moderate renal impairment in diabetic patients (estimated glomerular filtration rate \[GFR\] \< 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR \< 30 ml/min).
* Active bleeding, recent (\< 3 mo) GI bleeding, severe liver dysfunction, bleeding diathesis.
* Recent (\< 3 mo) internal eye surgery or hemorrhagic retinopathy; recent (\< 10 days) major surgery, cataract surgery, trauma, cardiopulmonary resuscitation, obstetrical delivery, or other invasive procedure.
* History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
* Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: patients with non-melanoma primary skin cancers are eligible to participate in the study.
* Severe hypertension on repeated readings (systolic \> 180 mmHg or diastolic \> 105 mmHg).
* Pregnant (positive pregnancy test, women of childbearing potential must be tested).
* Recently (\< 1 mo) had thrombolysis or is participating in another investigational drug study.
* Use of a thienopyridine antiplatelet drug (except clopidogrel) in the last 5 days.
* Life expectancy \< 2 years or chronic non-ambulatory status.
* Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Answer: B