Please select the eligibility criteria that correspond to the clinical trial below.
Title: The BERN Ultrasound-enhanced Thrombolysis for Ilio-Femoral Deep Vein Thrombosis versUs Standard Catheter Directed thromboLysis Trial (BERNUTIFUL-Trial)
Brief Summary: Patients with deep vein thrombosis (DVT) of the ilio-femoral veins have increased risk for developing post-thrombotic syndrome (PTS) and recurrent venous thromboembolism compared to more distal DVT. There's evidence that the early removal of the obstructing thrombus by catheter directed thrombolysis (CDT) reduces the risk of developing a PTS, and a higher degree of thrombolysis is associated with lower incidence of PTS, better quality of life and lower risk of recurrent venous thromboembolism. A further development is ultrasound-enhanced thrombolysis combining CDT with a sophisticated catheter system that employs high-frequency, low-dose ultrasound. In vitro experiments showed that adding ultrasound to thrombolytic drugs accelerates thrombolysis while Ultrasound exposure alone results in no thrombolysis, however the superiority of ultrasound-enhanced thrombolysis over standard CDT has never been formally assessed in vivo. The hypothesis for this study is that ultrasound-enhanced thrombolysis reaches a higher degree of thrombolysis than standard CDT in patients with symptomatic ilio-femoral DVT.


Options:
A: Inclusion criteria

* Any operation (elective or emergency) done in an operating theatre by a surgeon.
* All surgical specialties including: acute care surgery, breast surgery, cardiac surgery, colorectal surgery, general surgery, gynaecology, hepatobiliary surgery, neurosurgery, obstetrics, oesophagogastric surgery, ophthalmology, oral and maxillofacial surgery, orthopaedics, otolaryngology, paediatric surgery, plastic surgery, thoracic surgery, transplant surgery, trauma surgery, urology, vascular surgery.
* Day case surgery and inpatient surgery included.
* Any SARS-CoV-2 status (positive at any time, negative, not tested).
* All ages including children and adults.

Exclusion criteria:

Minor procedures (full list will be available in the protocol).
B: Inclusion Criteria:

* Symptomatic proximal DVT involving the iliac and/or common femoral vein, confirmed by Duplex Sonography, Angio-CT, Angio-MRI or Phlebography
* Written informed consent

Exclusion Criteria

* Age less than 18 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 post-thrombotic syndrome (PTS) or previous symptomatic DVT within the last 2 years.
* Limb-threatening circulatory compromise.
* PE with hemodynamic compromise (i.e., hypotension).
* Inability to tolerate catheter procedure due to severe dyspnea or acute systemic illness.
* Allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
* Known significant bleeding risk, or known coagulation disorder (including vitamin K antagonists with INR \> 2.0 and platelet count \< 100 000/mm3)
* Severe renal impairment (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, CPR, obstetrical delivery, or other invasive procedure.
* History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
* Severe hypertension on repeated readings (systolic \> 180 mmHg or diastolic \> 105 mmHg).
* Pregnant, lactation or parturition within the previous 30 days (positive pregnancy test, women of childbearing age must be tested or use a medically accepted method of birth control).
* Recently (\< 1 mo) had thrombolysis.
* Life expectancy \< 6 months or chronic non-ambulatory status.
* Participating in any other investigational drug or device study or previous enrollment in this study
* Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).
* Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated
C: Inclusion Criteria for Anticoagulation Hypothesis

1. Adult patients (≥18 years), with polymerase chain reaction (PCR)-confirmed COVID-19 admitted to ICU within 7 days of initial hospitalization , who do not have another firm indication for anticoagulation (such as mechanical valve, high-risk atrial fibrillation (AF), VTE, or left ventricle (LV) thrombus),who are not enrolled in another blinded randomized trial, and are willing to participate in the study and provide informed consent .
2. Estimated survival of at least 24 hours at the discretion of enrolling physician

Exclusion Criteria for Anticoagulation Hypothesis

1. Weight \<40 Kilogram (kg)
2. Overt bleeding at the day of enrollment
3. Known major bleeding within 30 days (according to the Bleeding Academic Research Consortium (BARC) definition, Appendix A)
4. Platelet count \<50,000/Fl
5. Pregnancy (as confirmed by Beta human chorionic gonadotropin (HCG) testing among female patients \<50 years)
6. Patients on Extracorporeal Membrane Oxygenation (ECMO)
7. History of heparin induced thrombocytopenia or immune thrombocytopenia
8. Ischemic stroke within the past 2 weeks
9. Craniotomy/major neurosurgery within the past 3 months
10. Major head or spinal trauma in the past 30 days
11. Known brain metastases or vascular malformations (aneurysm)
12. Presence of an epidural, spinal or pericardial catheter
13. Major surgery other than neurosurgery within 14 days prior to enrollment
14. Coexistence of severe obesity (weight \>120 kg or BMI\>35 kg/m2 along with severe renal insufficiency defined as creatinine clearance (CrCl) \<30 mL/sec)
15. Allergic reaction to study medications
16. Lack or withdrawal of informed consent

Inclusion Criteria for the Statin Randomization

1. Patients enrolled for the anticoagulation randomization
2. Willingness to participation in the study and providing informed consent

Exclusions Criteria for the Statin Randomization

1. Baseline liver function tests\> 3 times upper normal limits (ULN) or creatine kinase (CK) \>500 U/L
2. Active liver disease (LFT\>3 ULN plus histologic finding including cirrhosis or inflammation or necrosis)
3. Routine use of statins prior to the index hospitalization
4. Previous documented statin intolerance
D: Inclusion Criteria:

* BMI over 40
* Gastric banding or gastric bypass

Exclusion Criteria:

* Renal insufficiency
* Thrombopenia
* Long term anticoagulant treatment
* Pregnancy
* Allergy to heparin

Answer: B