RADIANCE-HTN Clinical Trial

 

RADIANCE-HTN is a multicenter, blinded, randomized (1:1), sham-controlled trial to evaluate the use of the Paradise Ultrasound Renal Denervation System to reduce ambulatory blood pressure in patients with mild-moderate hypertension (SOLO Cohort) and resistant hypertension (TRIO Cohort).  Both cohorts were individually powered for efficacy with a primary endpoint of daytime systolic ambulatory blood pressure (ABP) at 2 months (2M).

The study was conducted at over 50 centers in 7 countries (United States, United Kingdom, France, Germany, Netherlands, Belgium, and Poland), and 282 subjects were randomized.

SOLO (n=146)

  • Patients on 0-2 meds prior to enrollment
  • Off meds during screening and 2M primary analysis period
  • Confirmed hypertensive by ABP prior to randomization
  • 1º Endpoint: daytime systolic ABP @ 2M

VIEW SOLO RESULTS

TRIO (n=136)

  • Patients on ≥3 meds prior to enrollment
  • Standardized triple combination pill during screening and
    2M primary analysis period
  • Confirmed hypertensive by ABP prior to randomization
  • 1º Endpoint: daytime systolic ABP @ 2M

VIEW TRIO RESULTS


 

 

RADIANCE-HTN SOLO RESULTS

 

RADIANCE-HTN SOLO is a multicenter, international, blinded, randomised, sham-controlled trial to evaluate use of the Paradise Renal Denervation System to reduce ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications.

KEY TAKE-AWAYS

The Paradise Renal Denervation System lowered blood pressure in patients with hypertension who were randomized and followed for 2 months off medications, demonstrating:

  • Greater reduction in daytime ambulatory systolic BP than a sham procedure.
  • Consistent reductions in 24-hour ambulatory, office, and home BP.
  • Reduction of ≥5 mmHg observed in 66% of treated patients.
  • No major adverse events within 30 days of the procedure.

STUDY DESIGN

  • Trial was conducted at 21 centers in the USA and 18 in Europe.
  • 146 patients were randomized (1:1) to renal denervation or sham procedure (renal angiography)
    after a 4 week antihypertensive medication washout.
  • Primary Efficacy Endpoint: Change in Daytime Ambulatory Systolic BP at 2 Months.

Primary Endpoint:  Change in Daytime Ambulatory Systolic BP at 2 Months

*Between group difference adjusted for baseline blood pressure
**The per-protocol population omitted patients who started medications prior to end-point collection

Azizi et al. Lancet. 2018 Jun 9;391(10137):2335-2345.

ADDITIONAL FINDINGS

*Between group difference adjusted for baseline blood pressure
Azizi et al. Lancet. 2018 Jun 9;391(10137):2335-2345.

Azizi et al. Lancet. 2018 Jun 9;391(10137):2335-2345.

Average Hourly BP at Baseline and 2 Months Per Protocol

Azizi et al. ESH 2018.

RADIANCE-HTN TRIO is an international, multicenter, blinded, randomized (1:1), sham controlled study to evaluate the use of the Paradise Ultrasound Renal Denervation System for patients resistant to medical hypertension treatment. This is the first of its kind study, where all patients were placed on a standard triple anti-hypertensive therapy, then tested for sustained hypertension and randomized with sham control.

Key findings to be published soon

REFERENCES

 

Paradise Renal Denervation System Clinical Evidence

Azizi et al. Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control Following Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019;139:2542–2553.
https://pubmed.ncbi.nlm.nih.gov/30880441/

Daemen et al.  Safety and Efficacy of Endovascular Ultrasound Renal Denervation in Resistant Hypertension: 12-month Results From the ACHIEVE Study. J Hypertens. 2019;37(9):1906-1912.
https://pubmed.ncbi.nlm.nih.gov/31045964/

Fengler et al.  Predictors for profound blood pressure response in patients undergoing renal sympathetic denervation. J Hypertens. 2018 Jul;36(7):1578-1584.
https://www.ncbi.nlm.nih.gov/pubmed/29652730

Azizi et al.  Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018 Jun 9;391(10137):2335-2345.
https://www.ncbi.nlm.nih.gov/pubmed/29803590

Mauri et al.  A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs. Am Heart J. 2018 Jan;195:115-129.
https://www.ncbi.nlm.nih.gov/pubmed/29224639

Fengler et al.  Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience. J Hypertens. 2017 Jun;35(6):1310-1317.
https://www.ncbi.nlm.nih.gov/pubmed/28441700

Stiermaier et al.  Endovascular ultrasound for renal sympathetic denervation in patients with therapy-resistant hypertension not responding to radiofrequency renal sympathetic denervation. EuroIntervention. 2016 Jun 12;12(2):e282-9.
https://www.ncbi.nlm.nih.gov/pubmed/27290688

Daemen et al.  First-in-man radial access renal denervation with the ReCor Radiance catheter. EuroIntervention. 2015 Feb;10(10):1209-12.
https://www.ncbi.nlm.nih.gov/pubmed/25493912

Pathak et al. Renal sympathetic nerve denervation using intraluminal ultrasound within a cooling balloon preserves the arterial wall and reduces sympathetic nerve activity. EuroIntervention. 2015 Aug;11(4):477-84.
https://www.ncbi.nlm.nih.gov/pubmed/26298415

Fengler et al. A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN). Circulation. 2019 Jan 29;139(5):590-600.
https://pubmed.ncbi.nlm.nih.gov/30586691/

Sakakura et al. Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity EuroIntervention. 2015 Feb;10(10):1230-8.
https://pubmed.ncbi.nlm.nih.gov/25349043/

 

RENAL DENERVATION CLINICAL EVIDENCE AND BASIC SCIENCE

Böhm 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. Lancet. 2020;395(10234):1444–1451.
https://pubmed.ncbi.nlm.nih.gov/28859944/

Schmieder et al.  European Society of Hypertension position paper on renal denervation 2018. J Hypertens. 2018 Oct;36(10):2042-2048.
https://www.ncbi.nlm.nih.gov/pubmed/30015759

Schlaich et al.  Renal Denervation—Ready for Prime Time!? The Steep SPYRAL Stairs to RADIANCE in Hypertension Treatment. Hypertension. 2018 Aug;72(2):287-290
https://www.ncbi.nlm.nih.gov/pubmed/29941510

Kandzari 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. Lancet. 2018 Jun 9;391(10137):2346-2355.
https://www.ncbi.nlm.nih.gov/pubmed/29803589

Townsend et al.  Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017 Nov 11;390(10108):2160-2170.
https://www.ncbi.nlm.nih.gov/pubmed/28859944

Azizi et al.  Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015 May 16;385(9981):1957-65.
https://www.ncbi.nlm.nih.gov/pubmed/25631070

Völz et al.  Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation. J Hypertens. 2018 Jan;36(1):151-158.
https://www.ncbi.nlm.nih.gov/pubmed/29210862

Fengler et al.  Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic Hypertension. J Am Heart Assoc. 2017 May 17;6(5).
https://www.ncbi.nlm.nih.gov/pubmed/28515119

Kandzari et al.  The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. Am Heart J. 2016 Jan;171(1):82-91.
https://www.ncbi.nlm.nih.gov/pubmed/26699604

Mahfoud et al.  Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future. Eur Heart J. 2017 Nov 21;38(44):3272-3281.
https://www.ncbi.nlm.nih.gov/pubmed/28475773

Mahfoud et al.  Proceedings from the European clinical consensus conference for renal denervation: considerations on future clinical trial design. Eur Heart J. 2015 Sep 1;36(33):2219-27.
https://www.ncbi.nlm.nih.gov/pubmed/25990344

Sakakura et al.  Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity. EuroIntervention 2015; 10: 1230–8.
https://www.ncbi.nlm.nih.gov/pubmed/25349043