Ressource pédagogique : Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 - Lunch Session 3 : Regulatory viewpoint (Yuki ANDO)

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MODIGLIANI Lunch Debate Session 3 - Saturday December 1st, 2012: HEART FAILURE TRIALISTS WORKSHOP LEARNING FROM RECENT TRIALS AND SHAPING THE FUTURE OF HEART FAILURE TRIALS Chairpersons: Alexandre MEBAZAA, Paris, FRA - Christopher O’CONNOR, Durham, USA Webcast: Daniela DOBRE, Nancy, FRA Decreasing the very high mortality and rate of re-hospitalization associated with acute worsening HF is one of the most important unmet needs in cardiovascular medicine. Despite positive signals in Phase II studies, no drug has proven to reduce the appallingly high mortality or readmission rates. The reasons for these ‘failed’ trials are multiple, including the adequacy of candidate drugs, dosing, patient selection and disease characterization, and trial conduct. The phenotypes and pathophysiology of the syndrome are poorly understood. The syndrome is heterogeneous and the taxonomy is complex and remains without a consensus. Hospitalization for acute worsening HF is understood by some as the result of progressive worsening of chronic HF and by others as an entity which acuteness has been compared to what is acute coronary syndrome to chronic coronary artery disease. Some believe that hospitalizations for HF do not represent a distinct pathophysiology than chronic HF and could be better managed by the optimization of chronic HF neurohumoral therapy. On the other hand although there are no data to support that short-term in-patient therapeutic approach improves post-discharge clinical outcomes, some speculate that protecting the injured heart during the acute process might have long term benefit. Alleviating dyspnea is still considered by regulatory agents as an endpoint valid in itself, as far as there is no excess of deaths. However most patients improve with standard therapy and the magnitude of additional dyspnea relief by the investigational drug might be marginal and therefore hardly statistically detectable. Alternative ways to test for and/or quantify dyspnea have been investigated with the aim to define a dyspnea  measure that is more sensitive to change. RELAX-HF and ASTRONAUT are two trials whose results have just been announced. Both exemplify the issues highlighted here above. RELAX-HF is a phase II/III trial design trial of 48 hour IV infusion of relaxin for the treatment of signs and symptoms in patients hospitalized for acute decompensated HF (no EF criteria). ASTRONAUT evaluates the 6 months efficacy and safety of aliskiren therapy on top of standard therapy, on morbidity and mortality when initiated early after hospitalization for acute decompensated HF and low EF. Results of PRONTO are now available. PRONTO is a randomized trial comparing the potent and rapid acting calcium channel blocker Clevidipine vs. SOC for the ability to rapidly control blood pressure and provide dyspnea relief in acute heart failure patients. PRONTO examplifies yet another trial model: intervening within the first 2 hours after admission. Lessons learnt from RELAX-HF and PRONTO within the context of other recent trials in acute heart failure will be the main topic of brainstorming at this workshop, examining the potential change in paradigm in this area. The aim of this workshop is to learn from the PRONTO, RELAX-HF and ASTRONAUT experiences within the context of the other acute HF trials, understand the consequences of the results on the design of future trials, revision of regulatory guidlenes and on possible regulatory labeling on clinical practice. The various drug intervention options RELAX-HF, Omecamtiv mecarbil and other drug still on trial Speaker: Michael FELKER, Durham, USA ASTRONAUT Speaker: Aldo MAGGIONI, Florence, ITA Execution issues. Where best to screen and enroll patients? Overcoming variations in health care systems and globalization issues Speaker: Mihai GHEORGHIADE, Chicago, USA PRONTO: The merit and consequences of a very early intervention with an arterial vasodilator Speaker: Frank PEACOCK, Cleveland, USA Endpoint related issues. The value of dyspnea as an endpoint in acute HF, upon admission trials Speaker: Alexandre MEBAZAA, Paris, FRA The value of repeat events in post discharge hospitalized HF trials Speaker: Stuart POCOCK, London, GBR Regulatory viewpoint: Yuki ANDO, PMDA, JAP - Robert HEMMINGS, MHRA, GBR

"Domaine(s)" et indice(s) Dewey

• Maladies de l'appareil cardio-vasculaire (616.1)

Thème(s)