Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparing the Efficacy of Two Frequently Used Doses of Enoxaparin for VTE Prophylaxis After Bariatric Surgery
Brief Summary: Approximately two thirds of the adult population in developed countries is categorized as over-weight or obese (BMI\>30). In spite of worldwide increasing awareness, obesity is a major health concern. In the presence of numerous diets, medical therapies, and robust research, bariatric surgery remains the most effective means of weight reduction in morbidly obese patients (BMI\>40, or BMI\>35 with co-morbidities). However, bariatric surgery harbors a relatively high risk for postoperative complications; of them, venous thromboembolic events (VTE) are not common, but potentially lethal. Taken together with the propensity of morbidly obese patients to develop VTE, perioperative thromboprophylaxis is mandatory.

To date, low molecular weight heparins (LMWH) are most commonly used for VTE prophylaxis in the aforementioned population. Due to the pharmacologic properties of LMWH and the characteristics of surgically treated obese patients, the optimal dose that is to be utilized for VTE prophylaxis in this population remains unclear. Assessment of anti-FXa levels in the patients' plasma can be used in order to monitor LMWH activity. Levels of 0.2-0.5 U/ml have been proposed by some authors for VTE prophylaxis.

Few studies have compared different dosing regimens of enoxaparin (between 30mg-60mg q/12h) for VTE prophylaxis in the population undergoing bariatric surgery; nevertheless, these were small non- randomized trials, containing numerous methodological weaknesses. Hence, the optimal regimen of enoxaparin to be used for the prevention of VTE in the discussed population remains unclear.

The aim of the present study is to evaluate plasma levels of anti-FXa activity, comparing two most commonly used enoxaparin prophylactic regimens (40mg vs 60mg q/24h) in a large and homogenous cohort of sleeve gastrectomy patients. Although universally used by bariatric surgeons, the pharmacologic efficacy of these regimens has not been evaluated in patients undergoing bariatric surgery.


Options:
A: Inclusion Criteria:

* 3 days or less with clinical COVID-19 symptoms (fever, cough, sour throat, headache, body ache, anosmia, diarrhoea, vomiting).
* sign inform consent.
* \>50% risk developing a severe clinical presentation of COVID-19 according to risk calculator

Exclusion Criteria:

* COVID-19 negative test
* known pregnancy
* chronic use of steroid medication
* deep vein thrombosis in the last 6 months
* extended anticoagulation in the last 3 months.
* known allergy to sulodexide.
* severe symptoms that warrant hospital care at initial screening
B: Inclusion Criteria:

* Adult patient undergoing laparoscopic sleeve gastrectomy.
* The patient undergoes the surgery in the surgical wing of the Tel-Aviv Sourasky Medical Center.
* The patient has received full information regarding the studies nature, has agreed to participate and has given informed consent (documented by a signed informed consent form).

Exclusion Criteria:

* Patients with a previous Venous Thromboembolic Event.
* Patients requiring an IVC filter.
* Patients with known thrombophilia due to coagulation factor disorders (i.e factor V leiden).
* Patients with a bleeding disorder
* Patients with renal failure.
C: Inclusion Criteria:

A potential participant must have met all the following criteria to be included in the study:

1. Was hospitalized for laboratory-documented Coronavirus Disease 2019 (COVID-19) (e.g., positive for severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] via nasopharyngeal swab real time polymerase chain reaction \[RT-PCR; or other commercial or public health assay\]).
2. Was aged ≥18 years and ≤85 years.
3. Had a resting oxygen saturation (SaO2) of \<94% while breathing ambient air.
4. Had a score of 3 or 4 on the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale (required supplemental oxygen or non-invasive ventilation).
5. Had provided informed consent to participate in the study (by participant or legally-acceptable representative).

Exclusion Criteria:

A potential participant who met any of the following criteria was not eligible to participate in the study:

1. Was currently receiving invasive mechanical ventilation (e.g., via an endotracheal tube) (score of 2 on NIAID ordinal scale).
2. Had severe chronic respiratory disease, defined by any oxygen requirement prior to incident COVID-19.
3. Had active or uncontrolled bleeding at the time of randomization; a bleeding disorder, either inherited or caused by disease; history of known arterial-venous malformation, intracranial hemorrhage, or suspected or known cerebral aneurysm; or clinically significant (in the judgment of the Investigator) gastrointestinal bleeding within the 3 weeks prior to randomization.
4. Was receiving any other investigational (non-approved) therapy for the treatment of COVID-19 or participating in the treatment period of any other therapeutic intervention clinical study. Participating in the follow-up period of an interventional study may be permitted with prior medical monitor approval; participation in an observational study is permitted.
5. Was receiving systemic corticosteroids for a chronic condition.
6. Was receiving chronic anticoagulation with warfarin or direct oral anticoagulants (e.g., rivaroxaban, dabigatran, apixaban, edoxaban).
7. Was receiving or anticipated to require other systemic anticoagulation dosing at a therapeutic intensity. Prophylaxis of venous thromboembolism (VTE) using subcutaneous (SC) unfractionated heparin or enoxaparin was permitted with appropriate monitoring of coagulation status and within the guidelines described in the protocol.
8. Was receiving antiplatelet therapy, alone or in combination, including aspirin and other antiplatelet agents (e.g., clopidogrel, ticagrelor, and prasugrel), unless able to discontinue these agents at the time of randomization and was able to remain off these agents throughout the duration of the study intervention infusion period.
9. Had treatment with systemic (non-steroid) immunomodulators or immunosuppressant medications, including but not limited to tumor necrosis factor (TNF) inhibitors, anti-interleukin-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or 30 days (whichever was longer) prior to randomization.
10. Had a history of congestive heart failure requiring hospitalization.
11. Had active pericarditis (based on clinical assessment).
12. Had malignancy or other irreversible disease or condition for which 6-month mortality was estimated ≥50%.
13. Had a corrected QT interval (QTc) \>500 msec (or \>530-550 msec in participants with QRS greater than \>120 msec).
14. Had a Tisdale risk score ≥11 without the ability to monitor with serial electrocardiograms (ECGs) or telemetry.
15. Had severe renal impairment, as determined by calculated creatinine clearance \<30 mL/min or estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2.
16. Had alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values \>5x upper limit of normal (ULN).
17. Had activated partial thromboplastin time (aPTT) \>42 seconds.
18. Had thrombocytopenia with a platelet count \<80,000/mm3.
19. Had severe chronic liver disease (Child-Pugh Score of 10 to 15).
20. Had received dociparstat in a different clinical study.
21. Woman of childbearing potential who was pregnant, breastfeeding, and/or not using a highly-effective method of contraception (consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
22. Had evidence of clinical improvement in COVID-19 status including, but not limited to, a sustained reduction in oxygen requirements over the previous 48 hours, or extubated and/or no longer requiring mechanical ventilation following intubation for COVID-19.
23. Had any other condition, including abnormal laboratory values, that, in the judgment of the Investigator, could have put the participant at increased risk, or would have interfered with the conduct or planned analysis of the study.
D: Inclusion Criteria:

* Subject must be willing, understanding and able to provide written informed consent
* Subject must be a man or a woman with age \> 18 years at screening
* Subject must have an active moderate to severe COVID-19 confirmed by

  o A positive SARS-CoV-2 PCR test in the last 14 days
* At least one of the following features should be present

  * D-Dimer elevation \> 1.5 ULN (age adjusted cut-offs) AND/OR
  * Cardiac injury reflected by an elevation in hs-cTnT \> 2.0 upper limit of normal (ULN) AND at least one of the following conditions:

    * Known coronary artery disease (CAD)
    * Known diabetes mellitus
    * Active smoking
* A woman of childbearing potential must have a negative serum or urine pregnancy test before randomization occurs. Before randomization, a woman must be either:

  * Postmenopausal, defined as \>45 years of age with amenorrhea for at least 18 months,
  * If menstruating:

    * If heterosexually active, practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method \[(e.g., condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel)\], or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical studies, for the duration of their participation in the study, or
    * Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
    * Not heterosexually active

Exclusion Criteria:

* Subject has a very high bleeding risk: Any condition that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk of bleeding, such as, but not limited to, the following:

  * Any bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 1 months prior to randomization or occurring during index hospitalization.
  * Major surgery, biopsy of a parenchymal organ, ophthalmic surgery (excluding cataract surgery), or serious trauma (including head trauma) within 4 weeks before randomization.
  * A history of hemorrhagic stroke or any intracranial bleeding at any time in the past, evidence of primary intracranial hemorrhage on CT or magnetic resonance imaging scan of the brain, or clinical presentation consistent with intracranial hemorrhage. This applies as well to subjects hospitalized for ischemic stroke upon randomization.
  * Subject has a history of or current intracranial neoplasm (benign or malignant), cerebral metastases, arteriovenous (AV) malformation, or aneurysm.
  * Active gastroduodenal ulcer, defined as diagnosed within 1 months or currently symptomatic or known AV malformations of the gastrointestinal tract.
  * Platelet count \<90,000/μl at screening.
  * Patients with the diagnosis of bronchiectasis, that due to the investigator judgement are at an increased bleeding risk.
* Subject has any of the following diseases in the medical history:

  * Active cancer (excluding non-melanoma skin cancer) defined as cancer not in remission or requiring active chemotherapy or adjunctive therapies such as immunotherapy or radiotherapy. Chronic hormonal therapy (e.g. tamoxifen, anastrozole, leuprolide acetate) for cancer in remission is allowed.
  * Any medical condition (e.g. atrial fibrillation) that requires use of any therapeutic parenteral or oral anticoagulant(s) (e.g. warfarin sodium or other vitamin K antagonists, Factor IIa or FXa inhibitors, fibrinolytics) concomitantly with study medication.
  * Subject has known allergies, hypersensitivity, or intolerance to rivaroxaban or any of its excipients.
  * Baseline eGFR \<30 mL/min/1.73m2 calculated using CKD-EPI formula
  * Known significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) which is associated with coagulopathy or moderate or severe hepatic impairment.
  * Known HIV infection.
* Subject has undergone any of the following procedures or received any of the following drugs:

  * Received fibrinolysis during index hospitalization.
  * Use of antiplatelet therapy with prasugrel or ticagrelor up to 7 days prior to randomization. Other P2Y12 antagonists can be given. However, the use of concomitant antiplatelet therapy should be carefully considered. ASS \> 100 mg/d and continuous NSAIDs should be avoided.
  * Use of dual antiplatelet therapy, such as aspirin plus clopidogrel during the study.
* Subject is a woman who is pregnant or breast-feeding.
* Known intolerance or history of hypersensitivity to the active substance or to any of the excipients of the Investigational Medicinal Product (IMP)
* Subjects who are legally detained in an official institution.
* Subjects who may be dependent on the sponsor, the investigator or the trial sites, are not eligible to enter the trial.

Answer: B