Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI)

A randomised clinical trial

REGULATE-PCI Investigators

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Summary 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 13200 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 (

Original languageEnglish
Pages (from-to)349-356
Number of pages8
JournalThe Lancet
Volume387
Issue number10016
DOIs
Publication statusPublished - Jan 23 2016

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Percutaneous Coronary Intervention
Factor IXa
Randomized Controlled Trials
Hypersensitivity
Nucleotide Aptamers
Hemorrhage
Intention to Treat Analysis
Random Allocation
North America
Oligonucleotides
Multicenter Studies
Cause of Death
Stroke
Myocardial Infarction
bivalirudin
Safety
RB 006
RB 007

ASJC Scopus subject areas

  • Medicine(all)

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Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI) : A randomised clinical trial. / REGULATE-PCI Investigators.

In: The Lancet, Vol. 387, No. 10016, 23.01.2016, p. 349-356.

Research output: Contribution to journalArticle

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abstract = "Summary 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 13200 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 (",
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T2 - A randomised clinical trial

AU - REGULATE-PCI Investigators

AU - Lincoff, A. Michael

AU - Mehran, Roxana

AU - Povsic, Thomas J.

AU - Zelenkofske, Steven L.

AU - Huang, Zhen

AU - Armstrong, Paul W.

AU - Steg, P. Gabriel

AU - Bode, Christoph

AU - Cohen, Mauricio G.

AU - Buller, Christopher

AU - Laanmets, Peep

AU - Valgimigli, Marco

AU - Marandi, Toomas

AU - Fridrich, Viliam

AU - Cantor, Warren J.

AU - Merkely, B.

AU - Lopez-Sendon, Jose

AU - Cornel, Jan H.

AU - Kasprzak, Jaroslaw D.

AU - Aschermann, Michael

AU - Guetta, Victor

AU - Morais, Joao

AU - Sinnaeve, Peter R.

AU - Huber, Kurt

AU - Stables, Rod

AU - Sellers, Mary Ann

AU - Borgman, Marilyn

AU - Glenn, Lauren

AU - Levinson, Arnold I.

AU - Lopes, Renato D.

AU - Hasselblad, Vic

AU - Becker, Richard C.

AU - Alexander, John H.

PY - 2016/1/23

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N2 - Summary 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 13200 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 (

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