Design and Rationale of a Randomized Trial of COBRA PzF Stenting to REDUCE Duration of Triple Therapy (COBRA-REDUCE)

• Published in: Cardiovascular revascularization medicine Vol. 34; pp. 17 - 24
• Main Authors: Colleran, Róisín, Joner, Michael, Cutlip, Donald, Urban, Philip, Maeng, Michael, Jauhar, Rajiv, Barakat, Mark, Michel, Jonathan M., Mehran, Roxana, Kirtane, Ajay J., Maillard, Luc, Kastrati, Adnan, Byrne, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Brain Ischemia - etiology; Cobra PzF; Coronary stenting; Drug Therapy, Combination; Drug-eluting stent; Drug-Eluting Stents; High bleeding risk; Humans; Oral anticoagulation; Percutaneous coronary intervention; Percutaneous Coronary Intervention - adverse effects; Platelet Aggregation Inhibitors - adverse effects; Polymer-coated stent; Polyzene-F; Prospective Studies; Randomized; Short dual antiplatelet therapy; Stents; Stroke - diagnosis; Stroke - etiology; Stroke - prevention & control; Treatment Outcome; FDA; NOAC; Drug-eluting stent; ITT; Percutaneous coronary intervention; Coronary stenting; Oral anticoagulation; Short dual antiplatelet therapy; Polymer-coated stent; HBR; eCRF; Cobra PzF; PzF; DAPT; LOE; Polyzene-F; CAD; COR; High bleeding risk; BMS; VKA; BARC; OAC; ACS; DES; Randomized; PCI
• ISSN: 1553-8389; 1878-0938
• DOI: 10.1016/j.carrev.2021.01.022

A coronary stent with thromboresistant and pro-healing properties such as the polymer polyzene F-coated (COBRA PzF) stent might safely allow for a very short duration of triple therapy in patients taking oral anticoagulation (OAC) who undergo coronary stenting. The COBRA-REDUCE trial is a prospective, multinational, randomized, open-label, assessor-blinded trial. A total of 996 patients at high bleeding risk because of requirement for OAC (with a vitamin K antagonist or non-vitamin K antagonist for any indication) will be randomized at sites in the United States and Europe to treatment with the COBRA-PzF stent followed by very short duration (14 days) DAPT or a Food and Drug Administration (FDA)-approved new generation drug-eluting stent followed by guideline-recommended DAPT duration (3 or 6 months). Two co-primary endpoints will be tested at 6 months: a bleeding co-primary endpoint (bleeding academic research consortium [BARC] ≥2 bleeding beyond 14 days or after hospital discharge, whichever is later [superiority hypothesis]) and a thrombo-embolic co-primary endpoint (the composite of all-cause death, myocardial infarction, definite/probable stent thrombosis or ischaemic stroke [non-inferiority hypothesis]). The trial is registered at clinicaltrials.gov (NCT02594501). The COBRA-REDUCE trial will determine whether coronary stenting with the COBRA PzF stent followed by 14 days of clopidogrel will reduce bleeding without increasing thrombo-embolic events compared with FDA-approved DES followed by 3–6 months clopidogrel in patients taking OAC and aspirin. •The COBRA Polyzene-F (COBRA PzF, CeloNova BioSciences Inc. San Antonio, TX) stent is a thin strut cobalt-chromium alloy stent coated with a nano-thin layer (≤ 0.05 μm) of Polyzene-F – a durable inorganic polymer – with no elution of anti-restenotic drug.•The stent is designed to optimize the interface with blood proteins by preferentially binding serum albumin over fibrinogen, thus preventing activation of inflammatory cells and platelets.•Preclinical studies have shown increased thromboresistance and accelerated healing compared with contemporary high performance DES.•The hypothesis of the COBRA-REDUCE trial is that in patients at high bleeding risk because of oral anticoagulation (OAC) therapy after coronary stenting, the COBRA PzF stent followed by 14 days of DAPT will reduce bleeding without increasing thrombo-embolic events compared to FDA-approved DES followed by guideline-recommended (3–6 months) DAPT.•Patients undergoing PCI who are taking OAC (with a vitamin K antagonist or non-vitamin K antagonist for any indication) will be randomly allocated to treatment with the COBRA-PzF stent followed by very short duration (14 days) clopidogrel or a Food and Drug Administration (FDA)-approved new generation drug-eluting stent followed by 3 or 6 months of clopidogrel on a background of OAC and aspirin therapy in both treatment groups.•The COBRA-REDUCE trial is the first trial to investigate a novel polymer-coated stent without elution of antiproliferative drug in combination with 14 days of DAPT compared to guideline-recommended therapy in patients with an indication for long-term OAC who undergo coronary stenting.