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Clinical Trial
. 2013 Aug;34(31):2481-9.
doi: 10.1093/eurheartj/ehs232. Epub 2012 Aug 2.

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  1 , 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; RADAR Investigators
Collaborators, Affiliations
Clinical Trial

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 et al. Eur Heart J. 2013 Aug.

Abstract

Aims: We 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 results: Non-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.

Conclusion: At 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.

Keywords: Acute coronary syndromes; Anticoagulation reversal; REG1.

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Figures

Figure 1
Figure 1
The REG1 anticoagulation system, consisting of pegnivacogin (RB006) and its complementary controlling agent anivamersen (RB007).
Figure 2
Figure 2
Study flow.
Figure 3
Figure 3
Total and ACUITY major bleeding through a 30-day follow-up. The number and incidence of total and major modified ACUITY bleeding is shown.
Figure 4
Figure 4
Total and ACUITY major bleeding through hospital discharge. The number and incidence of total and major modified ACUITY bleeding is shown.
Figure 5
Figure 5
Incidence of the composite ischaemic endpoint (death, non-fatal myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia in the target vessel distribution) through a 30-day follow-up.
See this image and copyright information in PMC

References

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