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

Safe & Timely Antithrombotic Removal-Direct Oral Anticoagulants (STAR-D): Prospective, Multicenter, Double-blind, Randomized Study of Apixaban & Rivaroxaban Removal to Reduce Risk of Serious Bleeding in Urgent Cardiac Surgery Patients

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

Study Overview

• Status: Terminated
• Conditions: Blood Loss, Surgical; Blood Loss, Postoperative; Hemorrhage, Surgical; Hemorrhage Postoperative
• Intervention / Treatment: Device: Sham comparator; Device: DrugSorb-ATR system

Detailed Description

The Safe and Timely Antithrombotic Removal - Direct Oral Anticoagulants (DOACs) Apixaban & Rivaroxaban (STAR-D) study is a prospective, multicenter, double-blind, randomized study that evaluated the DrugSorb™-Antithrombotic Removal (ATR) device for removal of apixaban and rivaroxaban to reduce the likelihood of serious bleeding in patients undergoing urgent cardiothoracic surgery. The objectives were

• To demonstrate reductions in surgical and early post-surgical bleeding with the intraoperative use of DrugSorb-ATR in patients undergoing cardiothoracic surgery ≤36hrs since last apixaban or rivaroxaban dose.
• To demonstrate reductions in apixaban or rivaroxaban blood levels (Δ[DOAC]) with the intraoperative use of DrugSorb-ATR.
• To establish the safety of the intraoperative use of DrugSorb-ATR in the intended population.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami and its Miami Cardiac and Vascular Institute
    • Orlando, Florida, United States, 32803
      • Advent Health
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown/Emory School of Medicine
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Medical Center
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Virtua Health
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital, TriHealth, Inc
    • Cleveland, Ohio, United States, 44106
      • University Hospitals, Cleveland Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Plano, Texas, United States, 75093
      • Baylor Scott & White The Heart Hospital
  • Virginia
    • Richmond, Virginia, United States, 23219
      • VCU Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin - Madison
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female age 18 years or older, with documented full, written informed consent
2. 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:

1. >48hrs between last apixaban or rivaroxaban dose and start of CT surgery
2. Patients on low dose apixaban or rivaroxaban for prophylactic indications
3. Heart-lung transplant procedures
4. Procedures for ventricular assist device (i.e., implant or revision of left ventricular assist device [LVAD] or right ventricular assist device [RVAD])

5. Any of the below conditions that pose a known risk for increased bleeding

   1. Heparin induced thrombocytopenia
   2. Preoperative platelet count <50,000u/L
   3. Hemophilia
   4. International normalized ratio (INR) greater than or equal to 1.8
6. Prohibited concomitant antithrombotic medications as defined in the study protocol
7. Acute sickle cell crisis
8. Known allergy to device components
9. Active (untreated) systemic infection
10. History of major organ transplantation and those currently receiving immunosuppressive medication or who are profoundly immune suppressed
11. Women with positive pregnancy test during current admission or who are breast-feeding
12. Life expectancy <30 days
13. Inability to comply with requirements of the study protocol
14. Treatment with investigational drug or device within 30 days of current surgery
15. Previous enrollment in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control; Standard of care with Sham set-up	Device: Sham comparator; Sham comparator in similar position to the investigational device, but NOT integrated into the cardiopulmonary bypass (CPB) circuit
Experimental: DrugSorb-ATR Intervention; Standard of care + DrugSorb-ATR system	Device: DrugSorb-ATR system; Sorbent hemoperfusion system integrated into the cardiopulmonary bypass (CPB) circuit; 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
Direct Oral Anticoagulant (DOAC) Drug Removal: Apixaban and Rivaroxaban	Percent change in blood apixaban or rivaroxaban levels from pre coronary bypass (CPB), that is, start of device use to 30 min post CPB	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
Packed Red Blood Cell (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 Clinical Events Committee	Through to discharge from index hospitalization, on average 1-2 weeks
Incidence of Fatal Perioperative Bleeding	Deaths directly attributable to procedure-related bleeding.	Through to discharge from index hospitalization, on average 1-2 weeks

Collaborators and Investigators

• Sponsor: CytoSorbents, Inc
• Investigators: Principal Investigator: Michael J Mack, MD, Baylor Scott & White The Heart Hospital; Principal Investigator: C. M Gibson, MD, Beth Israel Deaconess Medical Center, The Baim Institute, and Harvard Medical School

Publications and helpful links

General Publications

• Tripathi R, Morales J, Lee V, Gibson CM, Mack MJ, Schneider DJ, Douketis J, Sellke FW, Ohman ME, Thourani VH, Storey RF, Deliargyris EN. Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent. Eur Heart J Cardiovasc Pharmacother. 2022 Dec 2;8(8):847-856. doi: 10.1093/ehjcvp/pvac036.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2021
• Primary Completion (Actual): January 29, 2024
• Study Completion (Actual): January 29, 2024

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical; Postoperative Hemorrhage
• Other Study ID Numbers: 2021-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes