Please select the eligibility criteria that correspond to the clinical trial below.
Title: Catheter-directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis, an Open Randomized, Controlled, Clinical Trial
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%.


Options:
A: Inclusion Criteria:

1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material)
2. Positive pressure ventilation (either non-invasive or invasive) from \> 24 hours
3. Invasive mechanical ventilation from \< 96 hours
4. P/F ratio \< 150
5. D-dimer level \> 6 x upper limit of local reference range
6. PCR \> 6 fold upper limit of local reference range

Exclusion Criteria:

1. Age \< 18 years
2. On-going treatment with anticoagulant drugs
3. Platelet count \<100.000/mmc
4. History of heparin-induced thrombocytopenia
5. Allergy to sodium enoxaparine or other LMWH, unfractionated heparin or metylprednisolone;
6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment
7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery
8. Chronic assumption or oral corticosteroids
9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available;
10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit";
11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition);
12. Lack or withdrawal of informed consent.
B: 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
C: Inclusion Criteria:

* Participants must be at high-risk for Coronavirus disease 2019 (COVID-19) disease progression by fulfilling at least one of the following criteria at screening:

  * Presence of chronic pulmonary disease, chronic obstructive pulmonary disease (COPD), pulmonary hypertension
  * Diabetes mellitus (type 1 or type 2), requiring oral medication or insulin for treatment
  * Hypertension, requiring at least one oral medication for treatment
  * Immunocompromised status due to disease (e.g., those living with human immunodeficiency virus with a cluster of differentiation 4 \[CD4\] T-cell count of \<200 per cubic millimeter \[mm\^3\])
  * Immunocompromised status due to medication (e.g., taking 20 milligram \[mg\] or more of prednisone equivalents a day, anti-inflammatory monoclonal antibody therapies, cancer therapies)
  * Any chronic disease that is associated with high risk for severe COVID in the opinion of the site investigator
  * Body mass index ≥35 Kilogram per square meter (kg/m\^2) (based on self-reported weight and height).
* Documented Severe Acute Respiratory Syndrome Coronavirus 2 positive diagnostic test of ≤7 days at the time of screening
* Symptomatic for COVID-19 for ≤72 hours at the time of screening (defined as having at least 2 of the following symptoms of COVID-19 that is of new onset or has worsened from baseline, and include fever, chills, myalgia, arthralgia, headache, fatigue, cough, sore throat, nasal congestion, anosmia, ageusia, nausea, vomiting, or diarrhea. If only two symptoms are present, they cannot both be anosmia and ageusia)
* Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the inform consent form and in this protocol
* Agree to participate in all remote, in-person or home visits as required in the protocol and provide updated contact information as necessary.
* Female of childbearing potential must agree to practice adequate contraception during the study

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

* Currently hospitalized or under immediate consideration for hospitalization at screening and Day 1
* Have new onset shortness of breath or increased shortness of breath from pre-COVID-19 (for people with known COPD) at screening and Day 1
* Hypoxemia (oxygen saturation \<94% in ambient air or oxygen saturation below pre-COVID-19 level for people with known COPD) at Day 1
* Require supplemental oxygen (new requirement or increase in requirement from pre-COVID-19 condition) at screening and Day 1
* Have a history of (in the past 3 months) or current active pathological bleeding
* Have a history of hemorrhagic stroke or intracranial hemorrhage
* Have a recent severe head trauma within 30 days which includes concussion, skull fracture or hospitalization for head injury
* Have known intracranial neoplasm, cerebral metastases, arteriovenous malformation or aneurysm
* Have history of pregnancy-related hemorrhage
* Have active gastroduodenal ulcer or other gastrointestinal bleeding diagnosed in the past 3 months
* Currently are in a hemodynamically unstable state
* Currently require thrombolysis or pulmonary embolectomy
* Have history of severe hypersensitivity reaction to Xarelto®
* Currently have a prosthetic heart valve
* Have known diagnosis of triple positive antiphospholipid syndrome
* Have known diagnosis of chronic kidney disease (stage IV or receiving dialysis)
* Have a history of thrombocytopenia or known platelet count \<100,000 cells/mm\^3
* Have history of bronchiectasis and pulmonary cavitation
* Have active cancer (e.g, receiving chemotherapy or treatment for complication of the active cancer)
* Had epidural or neuraxial anesthesia or spinal puncture in the past 2 weeks and plan to undergo these procedures during the study
* Had surgery in the past 4 weeks or plan to undergo surgery during the study
* Currently is pregnant or plans to become pregnant
* Currently is breastfeeding
* Share household with an enrolled participant in this study
* Co-enrollment in any clinical trial that includes prohibited procedures (spinal puncture or surgery) or that includes treatments within the same drug class as rivaroxaban or treatments for which co-administration with rivaroxaban are prohibited. Note that any co-enrollment other than this requires approval by the Sponsor. For any co-enrolled study, the total volume of blood samples collected across the studies should not exceed 275 milliliters (mL) in 4 weeks.
* Currently using and plan to use the following medications during the study

  * Rivaroxaban or drugs in the same class
  * Dual anti-platelets therapy
  * Other anticoagulants
  * Combined Permeability glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) inhibitors and inducers
D: 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

Answer: B