Safe and Timely Antithrombotic Removal - Direct Oral Anticoagulants Apixaban & Rivaroxaban (STAR-D)

Study Overview
=================
Brief Summary
-----------------
Prospective, Multicenter, Double-blind, Randomized, Study to Evaluate DrugSorb-ATR Removal of Apixaban and Rivaroxaban to Reduce Likelihood of Serious Bleeding in Patients Undergoing Urgent Cardiothoracic Surgery

Official Title
-----------------
Safe and Timely Antithrombotic Removal - Direct Oral Anticoagulants Apixaban & Rivaroxaban (STAR-D): A Prospective, Multicenter, Double-blind, Randomized, Study to Evaluate DrugSorb-ATR Removal of Apixaban and Rivaroxaban to Reduce Likelihood of Serious Bleeding in Patients Undergoing Urgent Cardiothoracic Surgery

Conditions
-----------------
Blood Loss, Surgical, Hemorrhage, Surgical, Hemorrhage Postoperative, Blood Loss, Postoperative

Intervention / Treatment
-----------------
* Device: Sham comparator
* Device: DrugSorb-ATR system


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female age 18 years or older, with documented full, written informed consent Requiring cardiothoracic (CT) surgery with cardiopulmonary bypass (CPB) within 36 hours from last dose of either apixaban or rivaroxaban (*note that patients must be taking apixaban or rivaroxaban for one of the following indications: a) reduction of stroke/systemic embolism in nonvalvular atrial fibrillation, or b) initial or extended treatment of venous thromboembolism) Exclusion Criteria: >48hrs between last apixaban or rivaroxaban dose and start of CT surgery Patients on low dose apixaban or rivaroxaban for prophylactic indications Heart-lung transplant procedures Procedures for ventricular assist device (i.e., implant or revision of LVAD or RVAD) Any of the below conditions that pose a known risk for increased bleeding Heparin induced thrombocytopenia Preoperative platelet count <50,000u/L Hemophelia INR greater than or equal to 1.8 Prohibited concomitant antithrombotic medications as defined in the study protocol Acute sickle cell crisis Known allergy to device components Active (untreated) systemic infection History of major organ transplantation and those currently receiving immunosuppressive medication or who are profoundly immune suppressed Women with positive pregnancy test during current admission or who are breast-feeding Life expectancy <30 days Inability to comply with requirements of the study protocol Treatment with investigational drug or device within 30 days of current surgery Previous enrollment in this trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control<br>Standard of care with Sham set-up | Device: Sham comparator<br>* Sham comparator in similar position to the investigational device, but NOT integrated into the cardiopulmonary bypass (CPB) circuit<br>|
| Experimental: DrugSorb-ATR Intervention<br>Standard of care + DrugSorb-ATR system | Device: DrugSorb-ATR system<br>* Sorbent hemoperfusion system integrated into the cardiopulmonary bypass (CPB) circuit<br>* Other names: Sorbent hemoperfusion system;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of perioperative bleeding | Incidence of clinically significant perioperative bleeding events, as evaluated by a ranked composite endpoint | Through the first 48 hours post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOAC drug removal: apixaban | Change in blood apixaban levels | Through 30 minutes post-CPB | 
| DOAC drug removal: rivaroxaban | Change in blood rivaroxaban levels | Through 30 minutes post-CPB | 
| Chest tube drainage | Drainage volume from all chest and mediastinal tubes | Through 24 hours post-operation | 
| Platelet transfusions (volume) | Total platelet transfusions (mL) during hospitalization | Through to discharge from index hospitalization, on average 1-2 weeks | 
| Platelet transfusions (units) | Total platelet transfusions (units) during hospitalization | Through to discharge from index hospitalization, on average 1-2 weeks | 
| PRBC transfusions (volume) | Total PRBC transfusions (mL) during hospitalization | Through to discharge from index hospitalization, on average 1-2 weeks | 
| PRBC transfusions (units) | Total PRBC transfusions (units) during hospitalization | Through to discharge from index hospitalization, on average 1-2 weeks | 
| Incidence of moderate, severe, and massive perioperative bleeding events | Perioperative bleeding events classified according to the Universal Definition of Perioperative Bleeding, and analyzed by class (Class 0, 1, 2, 3, 4) | Through the first day post-operation | 
| Surgical re-exploration for bleeding | All surgical re-explorations for excessive bleeding, as adjudicated by an independent CEC | Through to discharge from index hospitalization, on average 1-2 weeks | 
| Incidence of fatal perioperative bleeding | Deaths directly attributable to procedure-related bleeding, as adjudicated by an independent CEC | Through to discharge from index hospitalization, on average 1-2 weeks |