UMMS Affiliation
Department of Medicine, Division of Cardiovascular Medicine
Publication Date
2020-12-01
Document Type
Article
Disciplines
Cardiology | Cardiovascular Diseases
Abstract
OBJECTIVE: Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention.
Approach and Results: In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02-0.75); P=0.02.
CONCLUSIONS: In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials.
Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02561000.
Keywords
acute coronary syndrome, coronary artery disease, myocardial infarction, percutaneous coronary intervention, troponin
Rights and Permissions
© 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
DOI of Published Version
10.1161/ATVBAHA.120.315168
Source
Kuliopulos A, Gurbel PA, Rade JJ, Kimmelstiel CD, Turner SE, Bliden KP, Fletcher EK, Cox DH, Covic L; TRIP-PCI Investigators. PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2990-3003. doi: 10.1161/ATVBAHA.120.315168. Epub 2020 Oct 8. PMID: 33028101; PMCID: PMC7682800. Link to article on publisher's site
Journal/Book/Conference Title
Arteriosclerosis, thrombosis, and vascular biology
Related Resources
PubMed ID
33028101
Repository Citation
Kuliopulos A, Gurbel PA, Rade JJ, Kimmelstiel CD, Turner SE, Bliden KP, Fletcher EK, Cox DH, Covic L. (2020). PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Open Access Publications by UMMS Authors. https://doi.org/10.1161/ATVBAHA.120.315168. Retrieved from https://escholarship.umassmed.edu/oapubs/4489
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.