Medtronic has announced the six-month results from the full cohort of the SPYRAL HTN-ON MED clinical trial. The late-breaking data were presented at the American Heart Association (AHA) Scientific Sessions 2022 (5–7 November, Chicago, USA).
With this news, Medtronic has submitted the final module of the Symplicity Spyral premarket approval (PMA) package to the US Food and Drug Administration (FDA) for review and approval.
Subjects who were prescribed antihypertensive medications and were treated with the Medtronic Symplicity Spyral renal denervation (RDN) system had a statistically significant and clinically meaningful reduction in office-based systolic blood pressure (OSBP), a key secondary endpoint, compared to subjects 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) due to increased medications in the sham control group and the potential impacts of the COVID-19 pandemic on the clinical trial environment.
The study also included win ratio, a pre-specified 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 favour 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.
“The ON MED study demonstrated significant reductions in office-based blood pressure, the most commonly used measure in clinical practice. Additionally, we saw reductions in absolute blood pressure that were consistent with earlier RDN studies,” said David Kandzari (Piedmont Heart Institute and Cardiovascular Services, Atlanta, USA) and SPYRAL HTN-ON MED principal investigator.
“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 behaviour 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.”
SPYRAL HTN-ON MED is a global, randomised, sham-controlled trial investigating the blood pressure-lowering effect and safety of RDN with the radiofrequency (RF)-based Symplicity Spyral RDN system in hypertensive patients who have been prescribed up to three antihypertensive medications, including diuretics, calcium channel blockers, ACE/ARB inhibitors or beta blockers.
A total of 337 patients with uncontrolled hypertension were enrolled at 42 sites across the USA, Europe, Japan, Australia, and Canada, and were randomised 2:1 to RDN (n=205) versus sham control (n=132).
Results were as follows:
- The primary Bayesian efficacy endpoint of 24-hr 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 mmHg 24-hr systolic ABPM reduction in the RDN group versus 4.5 mmHg in the control group (treatment difference of -1.9 mmHg, p=0.119)
- 6.7 mmHg nighttime systolic ABPM reduction in the RDN group versus 3.0 mmHg in the control group (treatment difference of -3.7 mmHg, p=0.01)
- The study met the prespecified secondary endpoint, which was the change in OSBP from baseline to six-month follow-up between the RDN group (n=199) and the sham control group (n=126).
- Statistically significant 9.9 mmHg OSBP reductions in the RDN group versus a 4.9 mmHg reduction in the sham control group (treatment difference of -4.9 mmHg, p=0.001)
- The study met the primary safety endpoint, evaluating major adverse events at one month post-procedure, and renal artery stenosis at six months, pooled across the SPYRAL HTN-ON and OFF MED studies (p<0.001)
- RDN demonstrated a low incidence of procedure-related and clinical adverse events at six-months in the SPYRAL HTN-ON MED study specifically.
- The win ratio demonstrated significance in favour of RDN versus a sham procedure (p=0.005).
- Overall burden of medications was higher in the sham control group at six months (p=0.04).