Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 : Debate : What relevant endpoints in autonomic nerve modulation therapy trials? What kind/level of evidence? Targets to meet for approval (FDA, and in EU, beyond CE mark) and reimbursement

Title : Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 : Debate : What relevant endpoints in autonomic nerve modulation therapy trials? What kind/level of evidence? Targets to meet for approval (FDA, and in EU, beyond CE mark) and reimbursement
Investigator viewpoint: George BAKRIS, Chicago, USA - Ileana PIÑA, New York, USA
Regulatory viewpoint: Andrew FARB, FDA, USA
Industry viewpoint: Rob KIEVAL, CVRx, USA - Kenneth STEIN, Boston Scientific, USA
Abstract : Debate : What relevant endpoints in autonomic nerve modulation therapy trials? What kind/level of evidence? Targets to meet for approval (FDA, and in EU, beyond CE mark) and reimbursement
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9th Global Cardiovascular Clinical Trialists Forum • Paris 2012
HYPERTENSION TRIALIST WORKSHOP: AUTONOMIC MODULATION THERAPY
Chairpersons: George BAKRIS, Chicago, USA - Sverre E. KJELDSEN, Oslo, NOR
Resistant hypertension is usually defined as uncontrolled hypertension despite the intake of at least 3 antihypertensive drugs in full doses including a diuretic. Most investigators would also claim that this also implies 24-hours systolic blood pressure remaining above 135 (or 140) mmHg. Over the years some evidence has accumulated that raised sympathetic nervous system activity is involved in the pathogenesis of hypertension and particularly so in more severe hypertension.
- Ablation of the renal nerves located in the adventitia of renal arteries has emerged as a novel treatment modality and a catheter manufactured by Adrian/Medtronic has been CE approved in Europe based on one RCT (SYMPLICITY -2). A much larger trial is ongoing (SIMPICITY 3). Several other producers have applied for approval.
- CVRx have developed Barostim based on carotid baroreceptors stimulation and have gathered some early experience with encouraging results that led to CE mark.
- These techniques have rapidly been taken up in several countries including in a large number of centers in Germany.
- Beyond resistant hypertension, various devices providing autonomic modulation therapy are entering the clinical development stages also in heart failure, CKD and diabetes.
- Vagal stimulation developed by Medtronic (Biocontrol) and Boston Scientific are being tested in the INOVATE-HF and NECTAR-HF respectively in systolic heart failure.
- Spinal Cord stimulation is considered by many in small proof of concept trials (St Jude SCS HEART) (Medtronic DEFEAT-HF)
- Understanding the differences in the clinical and regulatory environments in the United States and Europe helps explain why much early device testing takes place outside of the United States, and why the introduction of new devices into clinical practice is usually significantly delayed in the United States when compared with Europe.
- Both phenomena are direct results of inherent differences in the criteria for approval and the process required to obtain approval. In particular, the European CE Mark process requires demonstration of safety only (and not efficacy) and relies heavily on non-governmental notified bodies to regulate the approval and post-approval process. In contrast, the approval of a new high-risk device in the United States requires demonstration of both safety and efficacy and is more highly regulated by a central governmental agency (CDRH/FDA).
The aim of this workshop is to assemble primary investigators of a number of important ongoing trials and discuss preliminary results, strengths and limitations of the current trials, efficacy and safety endpoint related issues, as well as issues related to optimal trial design, approvability and implementation into daily clinical practice.
Device companies: CVRx, Medtronic, St. Jude, Marquette, Boston Scientific, Vessix Vascular, ReCor Medical, Adrian, Biosense, Maya Medical.
Réalisation, production : Canal U/3S et CERIMES
Keyword : Cardiovascular Clinical Trialists, Paris, 2012, Cardiovascular prevention, cardiovascular pharmacology, modulation therapy