Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2016 Jan 23;387(10016):349-356.
doi: 10.1016/S0140-6736(15)00515-2. Epub 2015 Nov 5.

Effect of the REG1 Anticoagulation System Versus Bivalirudin on Outcomes After Percutaneous Coronary Intervention (REGULATE-PCI): A Randomised Clinical Trial

Affiliations
Randomized Controlled Trial

Effect of the REG1 Anticoagulation System Versus Bivalirudin on Outcomes After Percutaneous Coronary Intervention (REGULATE-PCI): A Randomised Clinical Trial

A Michael Lincoff et al. Lancet. .

Erratum in

  • Department of Error.
    Lancet. 2016 Mar 19;387(10024):1162. doi: 10.1016/S0140-6736(16)00712-1. Lancet. 2016. PMID: 27025336 No abstract available.

Abstract

Background: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding.

Methods: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions.

Findings: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002).

Interpretation: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin.

Funding: Regado Biosciences Inc.

Comment in

  • An anticoagulant too good to be true for revascularisation.
    Verheugt FWA. Verheugt FWA. Lancet. 2016 Jan 23;387(10016):314-315. doi: 10.1016/S0140-6736(15)00727-8. Epub 2015 Nov 5. Lancet. 2016. PMID: 26547098 No abstract available.
  • REGULATE-PCI trial--Author's reply.
    Lincoff AM, Alexander JH, Mehran R. Lincoff AM, et al. Lancet. 2016 Apr 9;387(10027):1510-1511. doi: 10.1016/S0140-6736(16)00694-2. Epub 2016 Apr 7. Lancet. 2016. PMID: 27115975 No abstract available.
  • REGULATE-PCI trial.
    Slade E, Hartley P, Heneghan C; COMPare project team. Slade E, et al. Lancet. 2016 Apr 9;387(10027):1510. doi: 10.1016/S0140-6736(16)30128-3. Epub 2016 Apr 7. Lancet. 2016. PMID: 27115976 No abstract available.

Similar articles

See all similar articles

Cited by 33 articles

See all "Cited by" articles

Publication types

MeSH terms

Associated data

Feedback