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

Not Applicable

Completed

Conditions: Blood Loss, Postoperative
Hemorrhage Postoperative
Blood Loss, Surgical
Hemorrhage, Surgical

Interventions: Device: Sham comparator
Device: DrugSorb-ATR system

Registration Number: NCT04976530

Lead Sponsor: CytoSorbents, Inc

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

Inclusion Criteria

Male or female 18 years of age or older, with documented full, written informed consent
Requiring cardiothoracic (CT) surgery with cardiopulmonary bypass (CPB) within two days of ticagrelor discontinuation (day of last dose = day 0)

Exclusion Criteria

CT surgery occurring 3 days or greater following ticagrelor discontinuation
Heart-lung transplant procedures
Procedures for implant or revision of left ventricular assist device (LVAD) or right ventricular assist device (RVAD)
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)
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Sham comparator	Standard of care with Sham set-up
DrugSorb-ATR Intervention	DrugSorb-ATR system	Standard of care + DrugSorb-ATR system

Primary Outcome Measures

Name	Time	Method
Incidence of Perioperative (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Modified Intent to Treat (mITT) Population	Through the first 48hrs post-operation	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.
Incidence of Perioperative (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Isolated Coronary Artery Bypass Grafting (I-CABG) Per Protocol (PP) Population	Through the first 48hrs post operation	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.
Incidence of Perioperative (Periop) Bleeding, Supplemental Primary Effectiveness Composite Endpoint, mITT Population	Through the first 48 hours post-operation	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.
Incidence of Perioperative (Periop) Bleeding, Supplemental Primary Effectiveness Composite Endpoint, I-CABG Per Protocol (PP) Population	Through the first 48hrs post-operation	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.

Secondary Outcome Measures

Name	Time	Method
Chest Tube Drainage, mITT Population	Through 12hrs post-operation	Drainage volume from all chest and mediastinal tubes
Chest Tube Drainage, i-CABG PP Population	Through 12hrs post-operation	Drainage volume from all chest and mediastinal tubes
Packed Red Blood Cell (PRBC) Transfusions (Units), mITT Population	From procedure start through to discharge from index hospitalization, on average 1-2 weeks	Total PRBC transfusions (units) during hospitalization in the mITT population
PRBC Transfusions, (Units) I-CABG PP Population	From procedure start through to discharge from index hospitalization, on average 1-2 weeks	Total PRBC transfusions (units) during hospitalization
Platelet Transfusions (Units), mITT Population	From procedure start through to discharge from index hospitalization, on average 1-2 weeks	Total Platelet transfusions (units) during hospitalization
Platelet Transfusions, (Units), I-CABG PP Population	From procedure start through to discharge from index hospitalization, on average 1-2 weeks	Total Platelet transfusions (units) during hospitalization

Trial Locations

Locations (29): MedStar Health Research Institute
🇺🇸
Washington, District of Columbia, United States
St. Michael's Hospital, Unity Health Toronto
🇨🇦
Toronto, Ontario, Canada
University of Iowa
🇺🇸
Iowa City, Iowa, United States
Baylor Scott & White The Heart Hospital Plano
🇺🇸
Plano, Texas, United States
New York University Langone Health
🇺🇸
New York, New York, United States
University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
Virtua Health
🇺🇸
Marlton, New Jersey, United States
Jersey Shore University Medical Center
🇺🇸
Neptune, New Jersey, United States
Emory University Hospital Midtown/Emory School of Medicine
🇺🇸
Atlanta, Georgia, United States
Lutheran Medical Group
🇺🇸
Fort Wayne, Indiana, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University Hospitals, Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
St. Boniface Hospital
🇨🇦
Winnipeg, Manitoba, Canada
The Medical College of Wisconsin, Inc.
🇺🇸
Milwaukee, Wisconsin, United States
Carilion Clinic
🇺🇸
Roanoke, Virginia, United States
Hamilton General Hospital, Hamilton Health Sciences Corporation
🇨🇦
Hamilton, Ontario, Canada
London Health Sciences Centre, University Hospital
🇨🇦
London, Ontario, Canada
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
Montreal Heart Institute
🇨🇦
Montréal, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval
🇨🇦
Québec, Quebec, Canada
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Vermont Medical Center
🇺🇸
Burlington, Vermont, United States
University of Mississippi
🇺🇸
Jackson, Mississippi, United States
University of California, Davis Medical Center
🇺🇸
Sacramento, California, United States
Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
VCU Medical Center
🇺🇸
Richmond, Virginia, United States
University of Wisconsin-Madison
🇺🇸
Madison, Wisconsin, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States