Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI

NCT03247738 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IIS CHI001 WIRB
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.

Conditions

ST Segment Elevation Myocardial Infarction; Percutaneous Coronary Intervention

Keywords

ticagrelor; cangrelor

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity Measured by VerifyNow PRU

  Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)

  30 minutes

Secondary Outcomes (1)

• Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)

  30 minutes

Study Arms (2)

Cangrelor

EXPERIMENTAL

Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours

Drug: Cangrelor

Placebo

PLACEBO COMPARATOR

Normal saline bolus and infusion for 2 hours

Other: Placebo

Interventions

Cangrelor DRUG

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Also known as: Kangreal

Cangrelor

Placebo OTHER

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with STEMI undergoing primary PPCI
• Age \> 18 years old

You may not qualify if:

• Inability to provide written informed consent
• Known history of prior intracranial bleeding
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in the prior 10 days
• Known allergies to aspirin, ticagrelor or cangrelor
• On treatment with oral anticoagulant
• Treatment with glycoprotein IIb/IIIa inhibitors
• Fibrinolytics within 24 hours
• Active bleeding
• High risk of bleeding
• Known platelet count \<80x106/mL
• Known hemoglobin \<10 g/dL
• Intubated patients (prior to randomization)
• Known creatinine clearance \<30 mL/minute or on hemodialysis.
• Known severe hepatic dysfunction
• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection

Sponsors & Collaborators

• University of Florida: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (2)

• Luker J, Kuhr K, Sultan A, Nolker G, Omran H, Willems S, Andrie R, Schrickel JW, Winter S, Vollmann D, Tilz RR, Jobs A, Heeger CH, Metzner A, Meyer S, Mischke K, Napp A, Fahrig A, Steinhauser S, Brachmann J, Baldus S, Mahajan R, Sanders P, Steven D. Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial. Circulation. 2019 Sep 24;140(13):1061-1069. doi: 10.1161/CIRCULATIONAHA.119.041320. Epub 2019 Aug 30.

  PMID: 31466479 DERIVED

• Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Circulation. 2019 Apr 2;139(14):1661-1670. doi: 10.1161/CIRCULATIONAHA.118.038317.

  PMID: 30630341 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

cangrelor

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Dominick J. Angiolillo
• Organization: University of Florida College of Medicine, Jacksonville

dominick.angiolillo@jax.ufl.edu

9042443933

Study Officials

• Dominick Angiolillo, MD, PhD

  University of Florida College of Medicine-Jacksonville

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: August 14, 2017
• Study Start: November 20, 2017
• Primary Completion: December 13, 2018
• Study Completion: December 13, 2018
• Last Updated: September 9, 2020
• Results First Posted: February 6, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)