TARGET BP I RCT Investigates Ablative System’s Peregrine Alcohol-Based Renal Denervation System

April 8, 2024—Findings from the TARGET BP I pivotal phase 3 randomized clinical trial (RCT) of the Peregrine renal denervation system (Ablative Solutions) met its primary endpoint of lowering blood pressure at 3 months as measured with a 24-hour ambulatory systolic blood pressure monitor. The Peregrine device uses dehydrated alcohol to deactivate certain nerves surrounding the kidneys’ arteries to control high blood pressure. Ablative Systems funded the trial.

David E. Kandzari, MD, presented the data at ACC.24, the American College of Cardiology (ACC)’s Annual Scientific Session held April 6-8 in Atlanta, Georgia. The study was simultaneously published online by Dr. Kandzari et al in Circulation.

Dr. Kandzari is Chief of the Piedmont Heart Institute and cardiovascular service line, Director of Interventional Cardiology at Piedmont Heart Institute, and Chief Scientific Officer for Piedmont Health Care in Atlanta, Georgia.

According to the press release from the ACC, the trial reported positive results overall; however, investigators said the full study findings present a more complicated picture the study. TARGET BP I is the largest RCT to date assessing alcohol-based technology for deactivating connections between the kidneys and the nervous system involved in regulating blood pressure.

“We saw a modest but statistically significant difference in the primary endpoint, but there were no significant differences in other measures of blood pressure, including office systolic or diastolic blood pressure,” commented Dr. Kandzari in the ACC press release. “Further, there were unexpectedly large reductions in blood pressure observed in the sham-control group that merit further study.”

The ACC press release noted that the FDA has approved several renal denervation technologies that are designed to deactivate the renal nerves that mediate hypertension via minimally invasive procedures using either radiofrequency energy or ultrasound energy. The Peregrine system is being assessed to learn if it results in more complete and effective denervation than the earlier technologies.

To test the system’s efficacy, the investigators randomly assigned 301 patients to receive either renal denervation with the Peregrine system or a sham procedure. Patients assigned to the sham procedure were given sedation or sensory deprivation so that they would not know whether they had undergone the ablation procedure or not.

At the start of the study, all patients had been prescribed between two and five blood pressure medications but still had high blood pressure.

High blood pressure was defined in the study as systolic blood pressure between 150 and 180 mm Hg and diastolic blood pressure above 90 mm Hg as measured in a doctor’s office, as well as an average systolic blood pressure between 135 and 170 mm Hg as measured with a 24-hour ambulatory blood pressure monitor.

As summarized in the ACC press release, at 3 months after the procedure, 24-hour ambulatory systolic blood pressure dropped by 10 mm Hg, on average, among patients who received renal denervation and by 6.8 mm Hg, on average, among those who received a sham procedure.

The between-group difference of 3.2 mm Hg was statistically significant in favor of renal denervation, thus meeting the trial’s primary endpoint. However, there were no significant differences between the two groups in terms of systolic or diastolic blood pressure as measured in a doctor’s office at three months, a surprising finding that investigators said was difficult to explain, reported ACC.

“Typically, if we observe reductions in one measure of blood pressure, we expect similar declines across the board in other measures,” stated Dr. Kandzari. “In this trial, meaningful reductions from baseline were achieved with renal denervation across all measures, but the potential difference is muted by large declines in the control group. There are still many unanswered questions coming from this study in terms of why we find the results that we do.”

The investigators further noted that it is also unclear why the study patients who received a sham procedure experienced such a substantial drop in blood pressure when they did not receive any additional intervention as part of this trial. Previous renal denervation trials have reported similar patterns with evidence that participants in those trials took their blood pressure medications more consistently during the trial than before it, which could account for the improvement.

In the TARGET BP I trial, investigators assessed medication adherence with blood and urine tests and did not see any particular differences in drug adherence between groups that would explain the finding.

Overall, they found that the ablation procedure appeared safe with no major clinical events, such as death, stroke, or hypertensive crisis. One patient experienced a small tear in a blood vessel during the procedure.

Finally, Dr. Kandzari advised that the investigators plan to work with FDA reviewers to assess what the trial results might mean from a regulatory perspective and determine next steps, reported the ACC press release.