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

Completed

• Conditions: Acute Coronary Syndromes
• Interventions: Other: Non-Interventional Study

• Registration Number: NCT02271022
• Lead Sponsor: AstraZeneca

Brief Summary

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.

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 Timeline

• Study First Submitted: 2014-10-10
• Study First Submitted QC: 2014-10-20
• Study First Posted: 2014-10-22
• Study Start: 2015-02-17
• Primary Completion: 2019-10-31
• Study Completion: 2019-10-31
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-30
• Last Update Posted: 2020-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1	Non-Interventional Study	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.

Primary Outcome Measures

Name	Time	Method
Bleeding rates within 30 days	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.
Composite and individual components of cardiovascular death, MI, and stroke	30 days	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.

Secondary Outcome Measures

Name	Time	Method
Time between administration of first upstream OAP agent and catheterization	30 days	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.
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	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.
Healthcare Resource Utilization	30 days	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.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Milwaukee, Wisconsin, United States