Clinical Trial Design Principles and Outcomes Definitions for Device-Based Therapies for Hypertension: A Consensus Document From the Hypertension Academic Research Consortium

David E Kandzari, Felix Mahfoud, Michael A Weber, Raymond Townsend, Gianfranco Parati, Naomi D L Fisher, Melvin D Lobo, Michael Bloch, Michael Böhm, Andrew S P Sharp, Roland E Schmieder, Michel Azizi, Markus P Schlaich, Vasilios Papademetriou, Ajay J Kirtane, Joost Daemen, Atul Pathak, Christian Ukena, Philipp Lurz, Guido Grassi, Martin Myers, Aloke V Finn, Marie-Claude Morice, Roxana Mehran, Peter Jüni, Gregg W Stone, Mitchell W Krucoff, Paul K Whelton, Konstantinos Tsioufis, Donald E Cutlip, Ernest Spitzer, David E Kandzari, Felix Mahfoud, Michael A Weber, Raymond Townsend, Gianfranco Parati, Naomi D L Fisher, Melvin D Lobo, Michael Bloch, Michael Böhm, Andrew S P Sharp, Roland E Schmieder, Michel Azizi, Markus P Schlaich, Vasilios Papademetriou, Ajay J Kirtane, Joost Daemen, Atul Pathak, Christian Ukena, Philipp Lurz, Guido Grassi, Martin Myers, Aloke V Finn, Marie-Claude Morice, Roxana Mehran, Peter Jüni, Gregg W Stone, Mitchell W Krucoff, Paul K Whelton, Konstantinos Tsioufis, Donald E Cutlip, Ernest Spitzer

Abstract

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Keywords: clinical trials; hypertension; outcomes; renal denervation.

Figures

Figure 1.
Figure 1.
Change in systolic blood pressure (mm Hg) after renal denervation in 6 prospective, randomized, sham-controlled trials. ABPM indicates ambulatory blood pressure measurement; BP, blood pressure; RADIANCE HTN SOLO, Study of the ReCor Medical Paradise System in Clinical Hypertension in Absence of Hypertension Medications; RADIANCE-HTN TRIO, Study of the ReCor Medical Paradise System in Clinical Hypertension in the Presence of a Stabilized, Single Pill, Triple, Fixed Dose Antihypertensive Medication Regimen; SYMPLICITY HTN-3 trial, Renal Denervation in Patients With Uncontrolled Hypertension; SPYRAL HTN-OFF MED, Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-Electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications; SPYRAL HTN-OFF PIVOTAL, Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-Electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications Pivotal; and SPYRAL HTN ON MED, Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-Electrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy. Adapted from references 15, 17–21.
Figure 2.
Figure 2.
Clinical investigation recommendations for novel devices for hypertension management. ABPM indicates ambulatory blood pressure measurement; BP, blood pressure; CKD, chronic kidney disease; HF, heart failure; HTN, hypertension; LVH, left ventricular hypertrophy; and MI, myocardial infarction.

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