A new renal denervation system (RDN) that uses dehydrated alcohol modestly but significantly lowered 24-hour ambulatory systolic blood pressure (SBP) at three months, compared to sham control, but no difference was seen between groups for office BP, according to the results of the TARGET BP I trial, presented during a Late-Breaking Clinical Trials session at ACC.24 and published simultaneously in Circulation.

The pivotal phase 3 trial, the largest to date to assess alcohol-based RDN, was conducted between May 2019 and April 2023 at 99 centers in nine countries. A total of 301 patients with uncontrolled or treatment-resistant hypertension (office SBP 150-180 mm Hg and diastolic BP pressure >90 mm Hg plus average SBP 135-170 mm Hg on 24-hour monitoring) were randomized to RDN with the Peregrine System (n=148) or a sham procedure (n=153). Their mean age was 56.1 years and about 74% were men.

At baseline, most patients were prescribed three or more antihypertensive medications. Mean 24-hour systolic/diastolic BP at baseline was 146.3/87.2 mm Hg for the RDN group and 146.2/87.6 mm Hg for the sham control group, with a corresponding mean office BP of 164.3/98.4 mm Hg and 163.9/100.0 for the RDN and sham control groups, respectively.

Results showed that the change in mean 24-hour ambulatory SBP at three months, the primary endpoint, was greater in the RDN group with a 10 mm Hg reduction compared with 6.8 mm Hg in the sham group, with a statistically significant between-group difference of 3.2 mm Hg (p=0.0487). Across prespecified subgroup, no differences were observed between groups. Additionally, no significant differences were found for the mean change in office SBP at three months, which were 12.7 mm Hg and 9.7 mm Hg lower in the RDN and sham, respectively (p=0.173).

During the study, in the RDN and sham control groups, no significant differences were seen between the groups for medication changes (five in each) or patient adherence at 8% and 9%. Overall, researchers said the ablation procedure appeared safe with no major clinical events, such as death, stroke or hypertensive crisis. One patient experienced an arterial dissection during the procedure.

"Typically, if we observe reductions in one measure of blood pressure, we expect similar declines across the board in other measures," said David E. Kandzari, MD, FACC, who presented the results and the study's lead author. "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 researchers plan on working with the U.S. Food and Drug Administration to assess the trial results and outline next steps.