SPYRAL HTN-OFF MED Results Encourage Medtronic to Pursue Renal Denervation Pivotal Trial
August 28, 2017—Medtronic announced that it will conduct a new renal denervation (RDN) pivotal trial after the positive first results from the sham-controlled SPYRAL HTN-OFF MED study in patients with high blood pressure were presented by the Co-Principal Investigator, Professor Michael Böhm, MD, at the European Society of Cardiology's ESC Congress 2017, held August 26–30 in Barcelona, Spain. The data were also published by Professor Raymond R. Townsend, MD, et al online ahead of print in The Lancet.
The company advised that it intends to continue consulting with its physician advisors and global regulatory authorities about these results so they can appropriately move forward with a pivotal trial design to ultimately support regulatory approval in the United States, Japan, and other countries where the technology is not currently available.
According to Medtronic, the SPYRAL HTN-OFF MED study investigators found that in data from the first 80 patients enrolled in the study at 3 months, there were statistically significant and clinically important blood pressure reductions in the patients treated with RDN across both office and ambulatory systolic and diastolic measurements.
The company noted that the study evaluated RDN in the absence of any antihypertensive medications compared to a sham-controlled population to isolate its effect on blood pressure reduction. Unlike the previous SYMPLICITY HTN-3 trial, in which patients self-reported adherence and change in medications occurred among 40% of patients, the SPYRAL HTN-OFF MED study limited that variability, as patients remained off their medication throughout the duration of the study as confirmed by serum and urine testing for antihypertensive medication.
The SPYRAL HTN-OFF MED study is part of Medtronic's SPYRAL HTN global clinical trial program and accompanies the SPYRAL HTN-ON MED study as one of the global, prospective, randomized, sham-controlled trials conducted simultaneously by hypertension experts and experienced interventionalists to investigate the impact of RDN both in the absence of and in the presence of antihypertensive medications. The clinical program utilizes Medtronic's next-generation RDN technology, which is composed of the flexible, 6-F guide catheter compatible Symplicity Spyral multielectrode RDN catheter and Symplicity G3 RDN RF radiofrequency generator. The Symplicity Spyral system is investigational in the United States and Japan.
As summarized by Medtronic, the initial 3-month data found that patients who underwent RDN had their office systolic blood pressure decline an average of 10 mm Hg, resulting in a 7.7-mm Hg difference with the patients in the sham control arm (P = .016), and their diastolic blood pressure declined an average of 5.3 mm Hg, resulting in a 4.9-mm Hg difference with the sham control arm (P = .008).
The company noted that a meta-analysis associated the decrease of 7.7 mm Hg in systolic blood pressure between the two groups with a relative risk reduction of approximately 20% for major cardiovascular events, including heart attack and stroke. The meta-analysis was published by Dena Ettehad, MSc, in the The Lancet (2016;387:957–967).
In SPYRAL HTN OFF-MED, the 24-hour systolic ambulatory blood pressure of RDN patients declined 5.5 mm Hg, resulting in a 5-mm Hg difference from the sham control arm (P = .041), and the diastolic ambulatory blood pressure declined 4.8 mm Hg, resulting in a 4.4-mm Hg difference from the sham control arm (P = .002). Additionally, there were no reported cases of new or worsening renal failure, vascular complications, or other major adverse events, confirming the safety of the RDN procedure—even with a revised procedural approach that extended ablations into the kidney’s branch arteries and an increase in total number of ablations compared with previous RDN trials.
The SPYRAL HTN-OFF MED study enrolled 353 patients who were either drug naïve or willing to discontinue medication for 4 months, with mild-to-moderate hypertension (office systolic blood pressure, ≥ 150 mm Hg and < 180 mm Hg) at 24 centers in the United States, Europe, Japan, and Australia. Before randomization, patients were required to stop taking their antihypertensive medication during a period of 3 to 4 weeks, known as a medication washout. During the washout period and the 3 months following randomization, patients were monitored to ensure their blood pressure would not exceed 180 mm Hg.
In addition to this difference in medication use between SPYRAL HTN-OFF MED and SYMPLICITY HTN-3, the aftermath of SYMPLICITY HTN-3 revealed new anatomical insights showing that renal nerves are easier to access when the catheter treats the renal artery segments located close to the kidney. Whereas SYMPLICITY HTN-3 only averaged five ablations in the main renal artery and no ablations in the branch arteries, the flexible design and low profile of the investigational Symplicity Spyral system achieved an average of 10 main renal artery ablations and 13 branch artery ablations per kidney, noted Medtronic.
In the company's press release, Prof. Böhm commented, “Based on the clinical results presented at ESC, we are confident that the SPYRAL HTN-OFF MED study has successfully demonstrated the treatment effect of RDN. With consistent and significant drops across ambulatory and office-based blood pressure—including both systolic and diastolic measurements—we are confident to be moving forward with a pivotal trial so that doctors and patients may have an alternative approach to lowering blood pressure.”
Prof. Townsend stated, “These results are extremely encouraging for the more than 50% of hypertension patients who become nonadherent to their medications within 1 year of initiating therapy. The societal implications are potentially huge as well, as high blood pressure contributes more than $500 billion in direct costs to our health care systems globally.”
The study's Co-Principal Investigator David E. Kandzari, MD, explained in the company's announcement, “After SYMPLICITY HTN-3, we learned a lot about the procedure itself, medication adherence, and which patients may have less response to the RDN procedure—these insights have been incorporated into the revised clinical approach in the SPYRAL HTN program. With this new approach and protocol design, coupled with new technology that allows more consistent circumferential treatment and easier access into the distal anatomy, based on these compelling results we are confident that we’ve appropriately addressed the issues in previous RDN trials.”