A Study To Determine the Efficacy and Safety of REG1 Compared to Bivalirudin in Patients Undergoing PCI (Regulate)

• ClinicalTrials.gov Identifier: NCT01848106
• Recruitment Status: Terminated
• First Posted: May 7, 2013
• Last Update Posted: October 23, 2014
• Sponsor: Regado Biosciences, Inc.
• Collaborators: The Cleveland Clinic; Duke Clinical Research Institute; Canadian VIGOUR Centre; Icahn School of Medicine at Mount Sinai; Parexel
• Information provided by (Responsible Party): Regado Biosciences, Inc.

Study Description

Brief Summary:

This study is designed to determine the efficacy of REG1 compared to bivalirudin in preventing periprocedural ischemic complications and major bleeding in patients undergoing PCI as a treatment for CAD. Bivalirudin has been studied in patients undergoing PCI in both ACS (NSTEMI and unstable angina [UA]) and elective PCI. In comparison to UFH, bivalirudin has shown similar rates of ischemic events while demonstrating a significant reduction in bleeding and an improved net clinical benefit.

Evidence from previous studies indicates that pegnivacogin represents an extremely potent, chemically unique anticoagulant that can be reversed by anivamersen across multiple populations (refer to Section 1.2.2). The question that still remains is whether Factor IX (FIX) inhibition by pegnivacogin can result in fewer ischemic events than a previously studied agent while active control with anivamersen can preserve the benefit of reduced bleeding. The purpose of this study is to evaluate REG1 in an adequately powered definitive study with an open-label, multi-center, active-controlled, randomized design to answer that question.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: pegnivacogin/anivamersen; Drug: Bivalirudin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Multi-Center, Active-Controlled, Parallel Group Study To Determine the Efficacy and Safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention
• Study Start Date: September 2013
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bivalirudin; Bivalirudin bolus and infusion	Drug: Bivalirudin; Other Name: Angiox, Angiomax
Experimental: Reg 1 (pegnivacogin/anivamersen); Bolus pegnivacogin plus anivamersen active control agent	Drug: pegnivacogin/anivamersen; Other Name: Reg 1 Anticoagulation System

Outcome Measures

Primary Outcome Measures :

1. Ischemic composite [ Time Frame: Day 3 ]
   The primary efficacy endpoint is the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 3.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The study population will consist of patients with CAD undergoing PCI. Three key subgroups will be included
2. Willing and able to sign an Institutional Review Board/Ethics Committee (IRB/EC) approved informed consent prior to any study-related activities;
3. Male or female age 18 or greater;
4. If female of childbearing potential, must have a negative urine or serum pregnancy test or be post-menopausal for at least 1 year prior to randomization. Females of childbearing potential must be practicing adequate birth control to be eligible. It is the Investigator's responsibility for determining whether the patient has adequate birth control for study participation;
5. Subject is able and willing to comply with the protocol and all study procedures

Exclusion Criteria:

1. Acute ST-segment elevation myocardial infarction within 48 hours of randomization;
2. Evidence of current clinical instability
3. Evidence of a contraindication to anticoagulation or increased risk of bleeding
4. Use of any investigational drug or device within 30 days of randomization or the planned use of an investigational drug or device through EOS (Day 30 follow-up);
5. Use of the select antithrombotic agents
6. Baseline hemoglobin (Hgb) <9 g/dL or equivalent;
7. Baseline estimated glomerular filtration rate (GFR) ≤ 10 mL/min/1.73m² or currently undergoing renal replacement therapy (hemodialysis or peritoneal dialysis);
8. Baseline platelet count <100,000/mm3;
9. Known allergy or intolerance to aspirin, to all available ADP/P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), or to bivalirudin or REG1 (or any of their respective components);
10. The following planned procedures: a. Planned staged PCI procedure within 3 days after randomization; b. Planned CABG or valve surgery within 30 days after randomization;
11. Any other medical or psychiatric condition that in the Investigator's judgment precludes participation in the study

Contacts and Locations

Locations

United States, South Dakota

Black Hills Cardiovascular Research

Rapid City, South Dakota, United States, 57701

Sponsors and Collaborators

Regado Biosciences, Inc.

The Cleveland Clinic

Duke Clinical Research Institute

Canadian VIGOUR Centre

Icahn School of Medicine at Mount Sinai

Parexel

Investigators

• Study Director: Steven L Zelenkofske, DO, FACC; Regado Biosciences
• Principal Investigator: A. Michael Lincoff, MD; The Cleveland Clinic
• Principal Investigator: Roxana Mehran, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: John H Alexander, MD, MHS; Duke Clinical Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

Lincoff AM, Mehran R, Povsic TJ, Zelenkofske SL, Huang Z, Armstrong PW, Steg PG, Bode C, Cohen MG, Buller C, Laanmets P, Valgimigli M, Marandi T, Fridrich V, Cantor WJ, Merkely B, Lopez-Sendon J, Cornel JH, Kasprzak JD, Aschermann M, Guetta V, Morais J, Sinnaeve PR, Huber K, Stables R, Sellers MA, Borgman M, Glenn L, Levinson AI, Lopes RD, Hasselblad V, Becker RC, Alexander JH; REGULATE-PCI Investigators. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. Lancet. 2016 Jan 23;387(10016):349-356. doi: 10.1016/S0140-6736(15)00515-2. Epub 2015 Nov 5. Erratum In: Lancet. 2016 Mar 19;387(10024):1162. Boudoulas, Dean [corrected to Boudoulas, Konstantinos D.].

• Responsible Party: Regado Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT01848106
• Other Study ID Numbers: REG1-CLIN310; 2013-001384-23 ( EudraCT Number )
• First Posted: May 7, 2013
• Last Update Posted: October 23, 2014
• Last Verified: October 2014

Keywords provided by Regado Biosciences, Inc.:

Percutaneous Coronary Intervention; Coronary Artery Disease; Acute Coronary Syndrome; Regado; Reg 1; bivalirudin

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Bivalirudin; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants