Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) (STAR-T)

Safe, Timely Antithrombotic Removal-Ticagrelor (STAR-T): Double-blind Randomized Study of Reduction in Bleeding by Ticagrelor Removal Via Intraop Use of DrugSorb-Antithrombotic Removal (ATR) in Cardiac Surgery Patients <2 Days of Drug Stop

Prospective, multi-center, double-blind, randomized pivotal trial to evaluate the safety and effectiveness of the DrugSorb-Antithrombotic Removal (ATR) system for intraoperative removal of ticagrelor in patients undergoing urgent cardiothoracic (CT) surgery with cardiopulmonary bypass (CPB).

Study Overview

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

Detailed Description

Antithrombotic agents such as ticagrelor can increase the risk of surgical bleeding in patients undergoing CT surgery if there is not adequate washout time of the drug. Patients who require urgent surgery may not be able to wait for the recommended washout time (up to 7 days). The intraoperative use of the DrugSorb-ATR device to remove active ticagrelor may help reduce the risk of postoperative surgical bleeding in these patients.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital, Hamilton Health Sciences Corporation
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre, University Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital, Unity Health Toronto
  • Quebec
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Québec, Quebec, Canada, G1V 4G5
      • Institut universitaire de cardiologie et de pneumologie de Quebec - Universite Laval
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown/Emory School of Medicine
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • 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
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi
  • 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
      • New York University Langone Health
  • Ohio
    • 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 Plano
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23219
      • VCU Medical Center
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic
  • 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 18 years of age or older, with documented full, written informed consent
2. Requiring cardiothoracic (CT) surgery with cardiopulmonary bypass (CPB) within two days of ticagrelor discontinuation (day of last dose = day 0)

Exclusion Criteria:

1. CT surgery occurring 3 days or greater following ticagrelor discontinuation
2. Heart-lung transplant procedures
3. Procedures for implant or revision of left ventricular assist device (LVAD) or right ventricular assist device (RVAD)
4. Pre-existing conditions that pose a known risk for bleeding (i.e., heparin induced thrombocytopenia /thrombosis [HITT], perioperative platelet count < 50,000u/L, hemophilia, and international normalized ratio [INR] >1.5)
5. Prohibited concomitant antithrombotic medications as defined in the study protocol
6. Acute sickle cell crisis
7. Known allergy to device components
8. Active (untreated) systemic infection
9. History of major organ transplantation and those currently receiving immunosuppressive medication or who are profoundly immune suppressed
10. Women with positive pregnancy test during current admission or who are breast-feeding
11. Life expectancy <30 days
12. Inability to comply with requirements of the study protocol
13. Treatment with investigational drug or device within 30 days of current surgery
14. 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 investigative device, but NOT integrated into the cardiopulmonary (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 (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Modified Intent to Treat (mITT) Population	Incidence of periop bleeding, primary effectiveness composite endpoint, mITT population. Primary effectiveness endpoint was a composite of (ranked) 1) fatal periop bleeding; 2) moderate, severe, or massive bleeding events based on the universal definition for periop bleeding (UDPB) >2 classification; and 3) 24 hour chest tube drainage (CTD) volume; evaluated by an unmatched win ratio method. Using the hierarchical order of the components of each composite endpoint every patient in the Sham arm is compared with every patient in the DrugSorb-ATR arm to make Ns x Nd pairs. The numbers below are the number of 'winners' for two treatments; 'win' is given for the better outcome in the pair, eg, less bleeding. The win ratio is the total number of winners in DrugSorb-ATR arm divided by the total number of winners in Sham arm. A ratio of wins > 1.0 favors the treatment arm. 95% confidence interval (CI) and p-value are calculated accordingly. The win ratio is 1.07 (95% CI 0.72, 1.58), p=0.748.	Through the first 48hrs post-operation
Incidence of Perioperative (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Isolated Coronary Artery Bypass Grafting (I-CABG) Per Protocol (PP) Population	Incidence of periop bleeding, primary effectiveness composite endpoint, i--CABG population. The primary effectiveness endpoint was a composite of (ranked) 1) fatal periop bleeding; 2) moderate, severe, or massive bleeding events based on the universal definition for periop bleeding (UDPB) >2 classification; and 3) 24 hour chest tube drainage (CTD) volume; evaluated by an unmatched win ratio method. Using the hierarchical order of the components of each composite endpoint every patient in the Sham arm is compared with every patient in the DrugSorb-ATR arm to make Ns x Nd pairs. The numbers below are the number of 'winners' for two treatments; 'win' is given for the better outcome in the pair, eg, less bleeding. The win ratio is the total number of winners in DrugSorb-ATR arm divided by the total number of winners in the Sham arm. A ratio of wins >1.0 favors the treatment arm. The win ratio was 1.33 (95% confidence interval 0.86, 2.04) p-value 0.202.	Through the first 48hrs post operation
Incidence of Perioperative (Periop) Bleeding, Supplemental Primary Effectiveness Composite Endpoint, mITT Population	Incidence of Periop Bleeding, Supplemental Primary Effectiveness Composite Endpoint, mITT population. The supplementary primary effectiveness endpoint was a composite of (ranked) 1) fatal periop bleeding; 2) severe, or massive bleeding events based on the universal definition for periop bleeding (UDPB) >3 classification; and 3) 24 hour chest tube drainage (CTD) volume; evaluated by an unmatched win ratio method. Using the hierarchical order of the components of each composite endpoint every patient in the Sham arm is compared with every patient in the DrugSorb-ATR arm to make Ns x Nd pairs. The numbers given below are the number of 'winners' for two treatments; a 'win' is given for the better outcome in the pair, eg, less bleeding. The win ratio is the total number of winners in DrugSorb-ATR arm divided by the total number of winners in Sham arm. A ratio of wins >1.0 favors the treatment arm. The win ratio was 1.17 (95% confidence interval 0.79, 1.73) p value 0.451.	Through the first 48 hours post-operation
Incidence of Perioperative (Periop) Bleeding, Supplemental Primary Effectiveness Composite Endpoint, I-CABG Per Protocol (PP) Population	Incidence of Periop Bleeding, Supplemental Primary Effectiveness Composite Endpoint, I-CABG population. The supplementary primary effectiveness endpoint was a composite of (ranked) 1) fatal periop bleeding; 2) severe, or massive bleeding events based on the universal definition for periop bleeding (UDPB) >3 classification; and 3) 24 hour chest tube drainage (CTD) volume; evaluated by an unmatched win ratio method. Using the hierarchical order of the components of each composite endpoint every patient in the Sham arm is compared with every patient in the DrugSorb-ATR arm to make Ns x Nd pairs. The numbers below are the number of 'winners' for two treatments; a 'win' is given for the better outcome in the pair, eg, less bleeding. The win ratio is the total number of winners in DrugSorb-ATR arm divided by the total number of winners in Sham arm. A ratio of wins >1.0 favors the treatment arm. The win ratio was 1.59 (95% confidence interval 1.02, 2.46) p-value 0.041.	Through the first 48hrs post-operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest Tube Drainage, mITT Population	Drainage volume from all chest and mediastinal tubes	Through 24hrs post-operation
Chest Tube Drainage, i-CABG PP Population	Drainage volume from all chest and mediastinal tubes	Through 24hrs post-operation
Chest Tube Drainage, mITT Population	Drainage volume from all chest and mediastinal tubes	Through 12hrs post-operation
Chest Tube Drainage, i-CABG PP Population	Drainage volume from all chest and mediastinal tubes	Through 12hrs post-operation
Packed Red Blood Cell (PRBC) Transfusions (Units), mITT Population	Total PRBC transfusions (units) during hospitalization in the mITT population	From procedure start through to discharge from index hospitalization, on average 1-2 weeks
PRBC Transfusions, (Units) I-CABG PP Population	Total PRBC transfusions (units) during hospitalization	From procedure start through to discharge from index hospitalization, on average 1-2 weeks
Platelet Transfusions (Units), mITT Population	Total Platelet transfusions (units) during hospitalization	From procedure start through to discharge from index hospitalization, on average 1-2 weeks
Platelet Transfusions, (Units), I-CABG PP Population	Total Platelet transfusions (units) during hospitalization	From procedure start 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; Principal Investigator: Richard Whitlock, MD, Hamilton General Hospital

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): August 31, 2021
• Primary Completion (Actual): August 7, 2023
• Study Completion (Actual): August 7, 2023

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 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: 2021-01

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