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

NCT04976530 | Completed Results DMC FDA Device

• 1 other identifier: 2021-01
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 29

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).

Conditions

Hemorrhage, Surgical; Blood Loss, Surgical; Blood Loss, Postoperative; Hemorrhage Postoperative

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Chest Tube Drainage, mITT Population

  Through 24hrs post-operation

• Chest Tube Drainage, i-CABG PP Population

  Through 24hrs post-operation

• 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

Study Arms (2)

Control

SHAM COMPARATOR

Standard of care with Sham set-up

Device: Sham comparator

DrugSorb-ATR Intervention

EXPERIMENTAL

Standard of care + DrugSorb-ATR system

Device: DrugSorb-ATR system

Interventions

DrugSorb-ATR system DEVICE

Sorbent hemoperfusion system integrated into the cardiopulmonary bypass (CPB) circuit

Also known as: Sorbent hemoperfusion system

DrugSorb-ATR Intervention

Sham comparator DEVICE

Sham comparator in similar position to the investigative device, but NOT integrated into the cardiopulmonary (CPB) circuit

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• CytoSorbents, Inc: lead

Study Sites (29)

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MedStar Health Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Emory University Hospital Midtown/Emory School of Medicine

Atlanta, Georgia, 30308, United States

Location

Lutheran Medical Group

Fort Wayne, Indiana, 46804, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

Virtua Health

Marlton, New Jersey, 08053, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

University Hospitals, Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor Scott & White The Heart Hospital Plano

Plano, Texas, 75093, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

VCU Medical Center

Richmond, Virginia, 23219, United States

Location

Carilion Clinic

Roanoke, Virginia, 24014, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

The Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226, United States

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Hamilton General Hospital, Hamilton Health Sciences Corporation

Hamilton, Ontario, L8L 2X2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences Centre, University Hospital

London, Ontario, N6A 5A5, Canada

Location

St. Michael's Hospital, Unity Health Toronto

Toronto, Ontario, M5B 1W8, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval

Québec, Quebec, G1V 4G5, Canada

Location

Related Publications (1)

• 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.

  PMID: 35657375 DERIVED

MeSH Terms

Conditions

Blood Loss, Surgical; Postoperative Hemorrhage

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Postoperative Complications

Limitations and Caveats

Ticagrelor blood levels comprise 99.8% protein-bound drug and 0.2% free, pharmacologically active drug. The device removes free ticagrelor and blood samples were collected during the study to assess reduction in free ticagrelor levels as a secondary endpoint. However, an assay that measures free ticagrelor is not commercially available and therefore data for free drug removal was not collected in the study.

Results Point of Contact

• Title: Weihong Fan
• Organization: CytoSorbents Corp

wfan@cytosorbents.com

732-329-8885

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 26, 2021
• Study Start: August 31, 2021
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: April 11, 2025
• Results First Posted: April 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7); US (22)