title: Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.
abstract: BACKGROUND
  Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation.
  
  
  METHODS
  We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints).
  
  
  RESULTS
  We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation.
  
  
  CONCLUSIONS
  Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits.
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria. Electronic address: thomas.lambert@akh.linz.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lambert
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nahler
authors.affiliation: 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria.
authors.forename: Miklos
authors.initials: M
authors.lastname: Rohla
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Reiter
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Grund
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kammler
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Blessberger
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kypta
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kellermair
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Starnawski
authors.affiliation: Clinic of Internal Medicine II - Department of Cardiology, Paracelsus Medical University of Salzburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.affiliation: 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weiss
authors.affiliation: 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Steinwender
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use; D001317:Austria; D001794:Blood Pressure / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D004351:Drug Resistance; D023381:Endpoint Determination / Q000145:classification / Q000379:methods; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney / Q000294:innervation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D017063:Outcome Assessment, Health Care; D012107:Research Design; D013562:Sympathectomy / Q000009:adverse effects / Q000379:methods
chemical_list: D000959:Antihypertensive Agents
keywords: Clinical trial design; Definition of treatment response; Endpoint design; Renal denervation; Resistant hypertension