A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: Results of the RADAR trial

Thomas J. Povsic, John P. Vavalle, Laura H. Aberle, Jaroslaw D. Kasprzak, Mauricio G. Cohen, Roxana Mehran, Christoph Bode, Christopher E. Buller, Gilles Montalescot, Jan H. Cornel, Andrzej Rynkiewicz, Michael E. Ring, Uwe Zeymer, Madhu Natarajan, Nicolas Delarche, Steven L. Zelenkofske, Richard C. Becker, John H. Alexander

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

AimsWe sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined.Methods and resultsNon-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively.ConclusionAt least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation. Clinical Trials Registration: ClinicalTrials.gov NCT00932100.

Original languageEnglish (US)
Pages (from-to)2481-2489
Number of pages9
JournalEuropean heart journal
Volume34
Issue number31
DOIs
StatePublished - Aug 14 2013

Keywords

  • Acute coronary syndromes
  • Anticoagulation reversal
  • REG1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: Results of the RADAR trial'. Together they form a unique fingerprint.

  • Cite this

    Povsic, T. J., Vavalle, J. P., Aberle, L. H., Kasprzak, J. D., Cohen, M. G., Mehran, R., Bode, C., Buller, C. E., Montalescot, G., Cornel, J. H., Rynkiewicz, A., Ring, M. E., Zeymer, U., Natarajan, M., Delarche, N., Zelenkofske, S. L., Becker, R. C., & Alexander, J. H. (2013). A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: Results of the RADAR trial. European heart journal, 34(31), 2481-2489. https://doi.org/10.1093/eurheartj/ehs232