Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Myocardial Infarction (UPSTREAM): An ED-Based Clinical Registry

The primary objective of the UPSTREAM Registry is to address the data gap regarding the course of NSTEMI (Non-ST-Elevation Myocardial Infarction)between ED (Emergency Department) arrival and diagnostic angiography in detail, by characterizing and following the ED and peri-ED use of advanced OAP (Oral Anti-Platelet) agents. In addition to exploring ED treatment patterns and success of both ischemic and bleeding risk stratification prior to definition of the coronary anatomy, data generated via the UPSTREAM registry will allow plausible attribution of ischemic and bleeding outcomes to pre-catheterization antiplatelet therapy in the management of NSTEMI. This registry further seeks to demonstrate that contemporary use of upstream ticagrelor is associated with an economically-sound utilization of hospital resources, and smooth transition of care into the outpatient, secondary prevention setting for the first 30 days after hospitalization. Finally, it will allow characterization of patient selection factors and processes for ticagrelor vs alternative OAP agents, carrying out that descriptive comparison through discharge. Patients transferred in to an UPSTREAM hospital are eligible for inclusion, but the timing for OAP agent administration and diagnostic catheterization begin with ED care at the first hospital.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndromes
• Intervention / Treatment: Other: Non-Interventional Study

Detailed Description

This is a Phase IV, post-approval, multicenter, prospective, noninterventional study of consecutive patients with a working diagnosis of NSTEMI (Non-ST-Elevation Myocardial Infarction) and treatment with an OAP (Oral Anti-Platelet) agent (ticagrelor, clopidogrel, or prasugrel) either in the ED (Emergency Department), or in any case within the timeframe that emergency physicians consider to be "upstream"- i.e., within the first 72 hours after ED arrival and at least 4 hours before diagnostic angiography. This registry is designed to address the data gap regarding the course of NSTEMI between ED arrival and diagnostic angiography in detail, by characterizing and following the ED and peri-ED use of advanced OAP agents.

Demographic, ischemic vs bleeding risk stratification [calculated retrospectively by GRACE (Global Registry of Acute Coronary Events), TIMI (Thrombolysis in Myocardial Infarction), and PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin) scores, and CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Bleeding Score, respectively], and OAP agent data (including, when discernible, rationale for agent selection) will be collected for all UPSTREAM patients, regardless of OAP therapy, through discharge. Risk factors, angiography results, intervention/s (if any), post-catheterization care, discharge regimens, and in-hospital outcomes will be recorded.

Patients who are treated upstream, in-hospital, and are discharged home on ticagrelor, will be further followed up, by telephone and/or chart review (if necessary elements are included in chart accessible to investigator), at 30 (+10) days post-discharge, during which evaluation data elements to be collected include patient-reported compliance with visits and medications, patient-reported healthcare resource utilization, and any pertinent events or complications.

Patients who are treated upstream, in-hospital, or discharged home on a different OAP therapy (clopidogrel or prasugrel) will not be followed beyond the data collection completed at hospital discharge. It is expected that a relatively small number of patients will change therapy from ticagrelor to another OAP agent after discharge and prior to 30 days post-discharge, though such changes will be queried in the 30-day call/chart review.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
    • Mobile, Alabama, United States, 36688
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Research Site
  • California
    • Sacramento, California, United States, 95812
      • Research Site
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Research Site
    • Hartford, Connecticut, United States, 06102
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32603
      • Research Site
    • Hialeah, Florida, United States, 33016
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
    • Tampa, Florida, United States, 33606
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Macon, Georgia, United States, 31217
      • Research Site
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Research Site
  • Indiana
    • Richmond, Indiana, United States, 47374
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
    • Baltimore, Maryland, United States, 21215
      • Research Site
    • Baltimore, Maryland, United States, 20814
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Worcester, Massachusetts, United States, 06105
      • Research Site
  • Michigan
    • Bloomfield, Michigan, United States, 48323
      • Research Site
    • Grand Blanc, Michigan, United States, 48439
      • Research Site
    • Royal Oak, Michigan, United States, 48073
      • Research Site
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Research Site
    • Saint Paul, Minnesota, United States, 55101
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
    • Kansas City, Missouri, United States, 64106
      • Research Site
    • Kansas City, Missouri, United States, 64116
      • Research Site
    • Springfield, Missouri, United States, 65807
      • Research Site
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Research Site
    • Flemington, New Jersey, United States, 08822
      • Research Site
    • Newark, New Jersey, United States, 07102
      • Research Site
    • Piscataway, New Jersey, United States, 08854
      • Research Site
    • Teaneck, New Jersey, United States, 07666
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11215
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
    • New York, New York, United States, 11235
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73135
      • Research Site
  • Oregon
    • Roseburg, Oregon, United States, 97471
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19141
      • Research Site
    • York And Ephrata, Pennsylvania, United States, 17403
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Research Site
    • Memphis, Tennessee, United States, 37920
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Research Site
    • Galveston, Texas, United States, 77550
      • Research Site
    • McKinney, Texas, United States, 75069
      • Research Site
    • New Braunfels, Texas, United States, 78132
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site
  • Wisconsin
    • Manitowoc, Wisconsin, United States, 54221
      • Research Site
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients (≥18 years of age) with a working diagnosis of NSTEMI and treatment with an OAP agent (ticagrelor, clopidogrel, or prasugrel) either in the ED, or in any case within the timeframe that emergency physicians consider to be "upstream"-within the first 72 hours of care and at least 4 hours before diagnostic angiography. In addition, only those patients who undergo a diagnostic coronary angiography within 72 hours of ED arrival will be eligible for UPSTREAM.

Description

Inclusion Criteria:

Patients (≥18 years of age) with a working diagnosis of NSTEMI and treatment with an OAP agent (ticagrelor, clopidogrel, or prasugrel) either in the ED, or in any case within the timeframe that emergency physicians consider to be "upstream"- i.e., within the first 72 hours of care and at least 4 hours before diagnostic angiography. In addition, only those patients who undergo a diagnostic coronary angiography within 72 hours of ED arrival will be eligible for UPSTREAM.

Exclusion Criteria:

1. Life expectancy less than 90 days in opinion of treating clinician;
2. Not undergoing diagnostic angiography within 72 hours of ED arrival;
3. Refusal of consent; or
4. Unlikely to comply with follow-up by telephone.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cohort 1; Patients (≥18 years of age) with a working diagnosis of NSTEMI and treatment with an OAP agent (ticagrelor, clopidogrel, or prasugrel) either in the ED, or in any case within the timeframe that emergency physicians consider to be "upstream"-within the first 72 hours of care and at least 4 hours before diagnostic angiography. In addition, only those patients who undergo a diagnostic coronary angiography within 72 hours of ED arrival will be eligible for UPSTREAM.

Other: Non-Interventional Study; Non-Interventional Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite and individual components of cardiovascular death, MI, and stroke	In patients who are treated upstream, in-hospital, and who are on ticagrelor at the end of 30-days post-discharge, composite and individual components of cardiovascular death, MI (Myocardial Infarction), and stroke, and bleeding rates will be assessed within 30 days.	30 days
Bleeding rates within 30 days	In patients who are treated upstream, in-hospital, and who are on ticagrelor at the end of 30-days post-discharge, bleeding occurring in-hospital will be classified according to the TIMI, GUSTO (Global Use of Strategies to Open Occluded Arteries), PLATO (PLATelet inhibition and patient Outcomes), and BARC (Bleeding Academic Research Consortium) scales; bleeding reported by the patient at 30-day follow-up will also be assessed.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Choice of alternative OAP agents in either the upstream setting or after switching from upstream ticagrelor to downstream or discharge clopidogrel or prasugrel will be explored and analyzed	Choice of alternative OAP agents in either the upstream setting or after switching from upstream ticagrelor to downstream or discharge clopidogrel or prasugrel will be explored and analyzed.	30 days
Time between administration of first upstream OAP agent and catheterization	Time between administration of first upstream OAP agent and catheterization will be analyzed as a continuous variable to assess more broadly the impact of OAP treatment prior to diagnostic angiography in NSTEMI.	30 days
Healthcare Resource Utilization	In patients who are treated upstream, in-hospital, and who are on ticagrelor at the end of 30-days post-discharge, healthcare resource utilization data will be captured throughout the 30 day continuum.	30 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Charles V. Pollack, MA, MD, FACEP, FAAEM, FAHA, Hospital Quality Foundation

Publications and helpful links

Helpful Links

• study report synopsis

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2015
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 22, 2014

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: NSTEMI; ACS, Acute Coronary Syndromes; MI, Myocardial Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Acute Coronary Syndrome
• Other Study ID Numbers: NIS-BRIL-UPSTREAM