Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation

Int J Cardiol. 2016 Oct 1:220:273-8. doi: 10.1016/j.ijcard.2016.06.110. Epub 2016 Jun 24.

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.

Conclusion: 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.

Keywords: Clinical trial design; Definition of treatment response; Endpoint design; Renal denervation; Resistant hypertension.

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Austria
  • Blood Pressure / physiology
  • Blood Pressure Monitoring, Ambulatory / methods
  • Drug Resistance
  • Endpoint Determination* / classification
  • Endpoint Determination* / methods
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Hypertension / surgery*
  • Kidney* / innervation
  • Kidney* / physiopathology
  • Male
  • Middle Aged
  • Observer Variation
  • Outcome Assessment, Health Care
  • Research Design
  • Sympathectomy* / adverse effects
  • Sympathectomy* / methods

Substances

  • Antihypertensive Agents