SPYRAL HTN Global Clinical Trial Program


Results with medications

This study evaluated the effect of the Symplicity™ blood pressure procedure in the presence of anti-hypertensive drugs.
Three-year follow-up
  • 18.7 mmHg reduction in 24-hour systolic ambulatory blood pressure (ABPM) for RDN patients versus baseline (p<0.01)2
  • 20.9 mmHg reduction in office systolic blood pressure2
  • >80% of patients taking meds achieved SBP <140 mmHg with the Symplicity procedure2
  • Zero device or procedural safety events2

Design details

  • Estimated enrollment: 340 participants
  • Study type: interventional (clinical trial)
  • Allocation: randomized
  • Intervention model: parallel assignment
  • Masking: single (participant)
  • Primary purpose: treatment
  • Actual study start date: July 2015

More details are available at clinicaltrials.gov.

Safety results at 3 years.

Adverse event (number of events) RDN
(n = 38)
Sham control
(n = 42)
All-cause death 0 1||
New myocardial infarction 0 0
New stroke 1 0
Hospitalization for hypertensive crisis / emergency 1 0
Sign. embolic event resulting in end-organ damage 0 0
Vascular complications 0 0
Major bleeding 0 0
Renal function    
New renal artery stenosis > 70% 0 0
Renal artery reintervention 0 0
Serum creatinine elevation >50% 0 0
New onset end stage renal disease 0 0
Table data2
|| One cardiovascular death occurred 693 days post-procedure. Patient was found unconscious at home; cause of death unknown.
¶ One patient had hypertension crisis and stroke at 427 days post-procedure. Patient presented to emergency department with weakness on left side and elevated BP 193/123 mmHg, received in-patient treatment, and was discharged in stable condition.

HTN-OFF MED trial design

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 PIVOTAL - SPYRAL HTN-OFF MED trial)

Trial data

The SPYRAL HTN-OFF MED pivotal trial met its secondary efficacy endpoint, showing clinically significant blood pressure reductions at three months.3† The powered efficacy endpoints for the trial were:

  • Change in 24-hour systolic blood pressure (SBP) at three months
  • Change in office SBP at three months

Zero major adverse events through three months in the RDN treatment arm.3

Patients enrolled in the SPYRAL HTN-OFF MED study were absent of their anti-hypertension medication. After the primary endpoint, medications were started/reintroduced by following a titration protocol.

Design details

  • Estimated Enrollment: 331 patients
  • Study Type: Interventional (Clinical Trial)
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Single (Participant)
  • Primary Purpose: Treatment
  • Actual Study Start Date: June 2015

More details are available at clinicaltrials.gov.

Safety results at 3 months

n (%) RDN
(n = 165)
Sham Control
(n = 165)
New myocardial infarction 0 0
New stroke 0 1 (0.6%)
Major Adverse Events 1 (0.6%) 0
  Death 0 0
  New onset end stage renal disease 0 0
  Sign. embolic event resulting in end-organ damage 0 0
  Renal artery perforation or dissection requiring intervention 0 0
  Vascular complications 0 0
  Hospitalization for hypertensive crisis/emergency 1 (0.6%) 0
Major bleeding (TIMI) 0 0
Serum creatinine elevation > 50% 0 0

Table Data2

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In typical uncontrolled hypertension patients.

An analysis of covariance model was used adjusting for baseline blood pressure.

Death, stroke, end-stage renal disease, or MI.


ANCOVA Adjusted; secondary efficacy analysis


Kandzari DE, Böhm M, Mahfoud F, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. The Lancet. 2018;391:2346–2355.


Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. The Lancet. 2022; 399:1401–1410.


Böhm M, Kario K, Kandzari DE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. The Lancet 2020; Published online March 29, 2020. DOI: 10.1016/ S0140–6736(20)30554-7.