• Worldwide RE-DUAL PCITM to enroll up to 8,500 patients with atrial fibrillation who have received a coronary stent1 • Data intended to help understand how to reduce blood clot risk and minimise bleeding risk in this patient population • Study is cooperatively conducted by the Harvard Clinical Research Institute and Boehringer Ingelheim
For Non-US/Non-UK/Non-Canadian Media
Ingelheim, Germany, 19 August, 2014 – Boehringer Ingelheim today announces that the first patients have been enrolled in the company’s new international phase III study, RE-DUAL PCI™.1 The study will evaluate the efficacy and safety of the oral anticoagulant dabigatran etexilate in patients with an irregular heartbeat called non-valvular atrial fibrillation (AF), who have undergone a percutaneous coronary intervention (PCI) with stent placement to widen their blocked coronary arteries.2 RE-DUAL PCITM aims to advance medical knowledge and guide future antithrombotic treatment choice for greatest patient benefit. It addresses the need for innovative new treatment regimens to improve patient prognosis.
AF is associated with a risk of stroke caused by blood clots from the heart.3 PCI, also known as angioplasty, is a medical procedure where a stent (a small mesh tube) is used to widen the arteries of the heart to restore or improve blood flow in patients with coronary artery disease.4 However the procedure is also associated with a risk of serious complications caused by blood clots, including stroke and other major adverse cardiac events.5,6 Patients with AF who undergo PCI are thus at special risk of these complications. To prevent them, patients receive antithrombotic therapy. Current standard care is linked to an increased risk of bleeding, because it currently involves taking three antithrombotic treatments together, one of them an anticoagulant.7
Professor Christopher Cannon
"Currently there are limited data about appropriate anticoagulation treatment in patients with AF undergoing PCI," said Professor Christopher Cannon, RE-DUAL PCITM Lead Investigator and Executive Director, Cardiometabolic Trials, Harvard Clinical Research Institute."We expect this study to provide data that can help us better understand how to prevent stroke and stent thrombosis while at the same time minimising bleeding risk in this especially vulnerable patient population," said Cannon, who also is a cardiologist at Brigham and Women’s Hospital in Boston and a Professor of Medicine, Harvard Medical School.
The RE-DUAL PCI™ study will compare the efficacy and safety of dual antithrombotic therapy with dabigatran etexilate (110mg or 150mg twice daily) plus clopidogrel or ticagrelor versus the currently recommended standard triple antithrombotic therapy regimen with warfarin (INR 2.0 – 3.0) plus clopidogrel or ticagrelor plus acetylsalicylic acid.2 The study will enroll approximately 8,500 patients at 700 sites in over 40 countries around the globe.1 Boehringer Ingelheim is conducting the study cooperatively with the Harvard Clinical Research Institute.
"Boehringer Ingelheim is confident in the ability of dabigatran etexilate to safely reduce the risk of thromboembolic events when used as directed and is committed to expanding the scientific knowledge of dabigatran use in AF patients who undergo significant procedures for their cardiac conditions," said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. "We look forward to the continuing enrollment of patients in RE-DUAL PCI™ and expect to have full results in 2017."
RE-DUAL PCI™ is part of Boehringer Ingelheim’s extensive clinical trial program, RE-VOLUTION™. With the recently announced RE-CIRCUIT™ and RE-SPECT ESUS™ studies, the entire programme will include 15 clinical trials involving over 60,000 patients in more than 100 countries globally.2,8-20
NOTES TO THE EDITORS
About PCI PCI, also known as angioplasty, is a medical intervention where stents are used to widen arteries of the heart.4 This intervention to restore or improve blood flow to the heart muscle is frequently undertaken in patients with an irregular heartbeat (AF) if they also have coronary artery disease.4,20 Worldwide, over one million AF patients may require the procedure each year.21
Patients with AF who undergo PCI with stenting are at increased risk of serious complications caused by blood clots, including stroke, systemic embolism, heart attacks, blood clots on the stents and even death.5,6 Long-term antithrombotic therapy is required to decrease patients’ risk of suffering blood clots and their consequences.
About RE-DUAL PCI™
Randomized Evaluation of DUAL Therapy with Dabigatran vs. Triple Therapy with Warfarin in Patients with NVAF that have Undergone PCI with Stenting
RE-DUAL PCITM will enroll approximately 8,500 patients at 700 sites in over 40 countries around the globe.1
The study has two primary endpoints, a composite efficacy endpoint and a safety endpoint. The composite efficacy endpoint is the time to death or first thrombotic event (all death, myocardial infarction, stroke or systemic embolism).2 The safety endpoint is the time to first major bleeding event, as defined by the International Society on Thrombosis and Haemostasis (ISTH).2
The estimated duration of the trial is 30 months.1 Because the trial protocol requires that the last patient entering the study receives at least six months of treatment, the earliest enrolled patients could be followed up to 30 months, the estimated duration of this event-driven trial.
About Pradaxa® (dabigatran etexilate) Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 3 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than 6 years and is approved in over 100 countries.1
Currently approved indications for Pradaxa® are:22,23
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
Treatment of DVT and PE and the prevention of recurrent DVT and PE in adults
Pradaxa®, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.22,24 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.25 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.24,26
Boehringer Ingelheim The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.
Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.
In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.
1Boehringer Ingelheim Data on File. 2Clinical Trials.gov. Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting. http://clinicaltrials.gov/ct2/show/NCT02164864?term=dabigatran+etexilate&recr=Open&rank=6 Last accessed July 2014. 3Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33(21):2719-47. 4Mayo Clinic. Coronary angioplasty and stents. http://www.mayoclinic.org/tests-procedures/angioplasty/basics/definition/prc-20014401 Last accessed July 2014. 5Faxon DP. et al. Consensus Document: Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting. Thromb Haemost. 2011;106:571–84. 6Chan W. et al. Impact of Periprocedural Atrial Fibrillation on Short-Term Clinical Outcomes Following Percutaneous Coronary Intervention. American Journal of Cardiology. 2012;109(4):471-477. 7DeWilde W. et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107–15. 8Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. 9Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-6. 10Connolly SJ, et al. The Long Term Multi-Center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) study. Circulation. 2013;128:237-43. 11Eriksson BI, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56. 12Eriksson BI, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost. 2011;105:721-9. 13Eriksson BI, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. Thromb Haemost. 2007;5:2178–85. 14Schulman S, et al. Dabigatran versus warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52. 15Schulman S, et al. Treatment of Acute Venous Thromboembolism with Dabigatran or Warfarin and Pooled Analysis. Circulation. 2014;129:764-772 16Schulman S, et al. Extended use of dabigatran, warfarin or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18. 17Oldgren J. et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32:2781-9. 18Diener H-C, et al. Rationale, objectives and design of a secondary stroke prevention study of dabigatran etexilate versus acetylsalicylic acid in patients with embolic stroke of undetermined source (RE-SPECT-ESUS). Presented at the European Stroke Conference, Nice, France on 7 May 2014, 12:45-14:15 PM. 19Ginsberg JS, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthoplasty. 2009;24:1–9. 20Boehringer Ingelheim Press Release - New Pradaxa® clinical study to explore practical management of patients with atrial fibrillation undergoing ablation. http://www.newshome.com/diru/news_releases/press_releases/2014/20_june_2014_dabigatranetexilate.html Last accessed August 2014. 21Lip G. et al. Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary—a Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2010.doi: 10.1093/eurheartj/ehq117 22Pradaxa® European Summary of Product Characteristics, 2014. 23PRADAXA® Prescribing Information, 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Last accessed: July 2014. 24Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95. 25Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40. 26Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.