Medtronic’s Symplicity Spyral RDN System Demonstrates Clinical Benefits in SPYRAL HTN-ON MED Trial

November 7, 2022—Medtronic announced the 6-month results from the full cohort of the SPYRAL HTN-ON MED clinical trial. The global randomized, sham-controlled trial is investigating the blood pressure lowering effect and safety of renal denervation (RDN) with the company’s radiofrequency-based Symplicity Spyral RDN system in hypertensive patients who have been prescribed up to three antihypertensive medications, including diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or β-blockers.

The data were presented as Late-Breaking Clinical Science at the American Heart Association Scientific Sessions 2022, held November 5-7 in Chicago, Illinois.

With this data, Medtronic has submitted the final module of the Symplicity Spyral premarket approval package to the FDA for review and approval.

The Symplicity Spyral RDN system is approved for commercial use in more than 60 countries around the world. The device is limited to investigational use in the United States, Japan, and Canada, advised Medtronic.

According to the company, patients in the study who were prescribed antihypertensive medications and were treated with the Symplicity Spyral RDN system had a statistically significant and clinically meaningful reduction in office-based systolic blood pressure (OSBP), a key secondary endpoint, compared to patients in the sham control group.

However, in the primary endpoint, RDN did not demonstrate a statistically significant reduction in 24-hour ambulatory systolic blood pressure (ABPM) because of increased medications in the sham control group and the potential impacts of the COVID-19 pandemic on the clinical trial environment, advised Medtronic.

The company noted that the study included Win Ratio, a prespecified secondary endpoint that combines reduction in blood pressure with reduction in medication burden, which enables assessment of the overall beneficial effect of RDN. The Win Ratio demonstrated significance in favor of RDN versus a sham procedure.

Finally, the study met its primary safety endpoint with a low incidence of procedure-related and clinical adverse events.

David Kandzari, MD, who is Chief, Piedmont Heart Institute and Cardiovascular Services in Atlanta, Georgia, serves as lead Principal Investigator of the SPYRAL HTN-ON MED trial.

“The ON MED study demonstrated significant reductions in office-based blood pressure, the most commonly used measure in clinical practice,” commented Dr. Kandzari in Medtronic’s press release. “Additionally, we saw reductions in absolute blood pressure that were consistent with earlier RDN studies.”

Dr. Kandzari continued, “Surprisingly, 24-hour ABPM declined with RDN but did not differ from the sham group, and the primary endpoint was not met. More than 80% of patients in the ON MED expansion group experienced follow up during the COVID-19 pandemic. Compared with patients enrolled before the pandemic, significant differences in baseline 24-hour ABPM were observed that may reflect changes in patient behavior and lifestyle during the pandemic. Additionally, patients treated with the sham procedure increased the amount of medication they were taking compared to those treated with RDN. These factors likely contributed to the smaller than expected differences in ABPM.”

As summarized in the Medtronic press release, the study enrolled 337 patients with uncontrolled hypertension at 42 sites across the United States, Europe, Japan, Australia, and Canada. The patients were randomized 2:1 to RDN (n = 205) versus sham control (n = 132).

The company reported the following results:

• The primary Bayesian efficacy endpoint of 24-hour systolic ABPM reduction was not met, with a 51% probability of superiority for the RDN group versus those who received a sham control procedure. However, nighttime systolic ABPM reduction was statistically significant.
  • 6.5 mm Hg 24-hour systolic ABPM reduction in the RDN group versus 4.5 mm Hg in the control group (treatment difference of –1.9 mm Hg; P = .119)
  • 6.7 mm Hg nighttime systolic ABPM reduction in the RDN group versus 3.0 mm Hg in the control group (treatment difference of –3.7 mmHg; P = .01)
• The study met the prespecified secondary endpoint, which was the change in OSBP from baseline to 6-month follow-up between the RDN group (n = 199) and the sham control group (n = 126).
  • Statistically significant 9.9 mm Hg OSBP reductions in the RDN group versus a 4.9 mm Hg reduction in the sham control group (treatment difference of –4.9 mm Hg; P = .001)
• The study met the primary safety endpoint, evaluating major adverse events at 1-month postprocedure, and renal artery stenosis at 6 months, pooled across the SPYRAL HTN-ON and OFF MED studies (P < .001).
  • RDN demonstrated a low incidence of procedure-related and clinical adverse events at 6-months in the SPYRAL HTN-ON MED study, specifically.
• The Win Ratio demonstrated significance in favor of RDN versus a sham procedure (P = .005).
• Overall burden of medications was higher in the sham control group at 6 months (P = .04).