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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- CytoSorbents, Inc
- Enrollment
- 140
- Locations
- 57
- Primary Endpoint
- Incidence of Perioperative (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Modified Intent to Treat (mITT) Population
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Incidence of Perioperative (Periop) Bleeding, Primary Effectiveness Composite Endpoint, Modified Intent to Treat (mITT) Population
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- Chest Tube Drainage, mITT Population(Through 12hrs post-operation)
- Chest Tube Drainage, i-CABG PP Population(Through 12hrs post-operation)
- Packed Red Blood Cell (PRBC) Transfusions (Units), mITT Population(From procedure start through to discharge from index hospitalization, on average 1-2 weeks)
- PRBC Transfusions, (Units) I-CABG PP Population(From procedure start through to discharge from index hospitalization, on average 1-2 weeks)
- Platelet Transfusions (Units), mITT Population(From procedure start through to discharge from index hospitalization, on average 1-2 weeks)
- Platelet Transfusions, (Units), I-CABG PP Population(From procedure start through to discharge from index hospitalization, on average 1-2 weeks)