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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.

Publication ,  Journal Article
Kuliopulos, A; Gurbel, PA; Rade, JJ; Kimmelstiel, CD; Turner, SE; Bliden, KP; Fletcher, EK; Cox, DH; Covic, L; TRIP-PCI Investigators,
Published in: Arterioscler Thromb Vasc Biol
December 2020

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.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

December 2020

Volume

40

Issue

12

Start / End Page

2990 / 3003

Location

United States

Related Subject Headings

  • United States
  • Treatment Outcome
  • Time Factors
  • Thrombosis
  • Stents
  • Recurrence
  • Receptor, PAR-1
  • Prospective Studies
  • Proof of Concept Study
  • Platelet Aggregation Inhibitors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kuliopulos, A., Gurbel, P. A., Rade, J. J., Kimmelstiel, C. D., Turner, S. E., Bliden, K. P., … TRIP-PCI Investigators, . (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. Arterioscler Thromb Vasc Biol, 40(12), 2990–3003. https://doi.org/10.1161/ATVBAHA.120.315168
Kuliopulos, Athan, Paul A. Gurbel, Jeffrey J. Rade, Carey D. Kimmelstiel, Susan E. Turner, Kevin P. Bliden, Elizabeth K. Fletcher, Daniel H. Cox, Lidija Covic, and Lidija 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 40, no. 12 (December 2020): 2990–3003. https://doi.org/10.1161/ATVBAHA.120.315168.
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.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

December 2020

Volume

40

Issue

12

Start / End Page

2990 / 3003

Location

United States

Related Subject Headings

  • United States
  • Treatment Outcome
  • Time Factors
  • Thrombosis
  • Stents
  • Recurrence
  • Receptor, PAR-1
  • Prospective Studies
  • Proof of Concept Study
  • Platelet Aggregation Inhibitors