RADIANCE-HTN TRIO Trial Demonstrates Effectiveness of Renal Denervation for Medication-Resistant Hypertension

May 16, 2021—In the international RADIANCE-HTN TRIO trial of the Paradise renal denervation (RDN) system (ReCor Medical, Inc.), patients with high blood pressure who did not respond to treatment with multiple medications had a greater reduction in daytime systolic blood pressure at 2 months after undergoing RDN than patients who did not receive RDN, with no difference in major adverse effects. ReCor Medical, which funded the study, received FDA Breakthrough Device designation for the Paradise RDN system in December 2020.

“This study has shown for the first time that RDN can effectively lower blood pressure in patients in whom it is uncontrolled despite standardized treatment with three guideline-recommended medications,” commented Coprincipal Investigator Professor Ajay Kirtane, MD, in a press release from the American College of Cardiology (ACC). Dr. Kirtane is Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and an interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center in New York, New York. Dr. Kirtane added, “RDN offers an additional tool that we could use to help these patients, hopefully achieving better overall control of hypertension, especially if longer-term data support the durability and safety of the procedure.”

Dr. Kirtane presented the findings virtually at ACC.21, the ACC’s 70th annual scientific sessions. The study was simultaneously published online by Michel Azizi, MD, et al in The Lancet.

According to the ACC announcement, patients in the trial who received RDN saw a median reduction of 8 mm Hg in daytime ambulatory systolic blood pressure compared with their level prior to treatment. The patients also had a 4.5 mm Hg greater drop in median blood pressure compared with those who received the sham procedure, despite both groups receiving the same three guideline-recommended antihypertensive medications as background therapy. The benefit of RDN was consistent regardless of sex, ethnicity, age, waist size, or blood pressure level at study entry.

The background of the study is that overactivity of the sympathetic nerves in the kidneys can contribute to high blood pressure. RDN works by delivering ultrasound-based energy that decreases the overactivity of these nerves. Other studies in patients with less severe hypertension have shown that compared with a sham procedure, RDN reduces blood pressure.

As summarized by ACC, the RADIANCE-HTN TRIO trial enrolled 989 patients in the United States, the United Kingdom, and five European countries. The patients’ average age was 53 years, and 80% were men.

At study entry, patients were taking an average of four antihypertensive medications. Despite this, patients’ average blood pressure at study entry was 163/104 mm Hg. Patients’ median body mass index was approximately 32.7. Approximately a quarter of patients also had type 2 diabetes.

At enrollment in the study, all patients were switched from their existing medications to a regimen consisting of three blood pressure–lowering medications combined into a single pill taken once daily. The use of such once-daily combination pills has been shown to improve patient adherence to blood pressure–reducing medication, noted the ACC. After 4 weeks on the once-daily, three-drug regimen, patients whose blood pressure was still 135/85 mm Hg or higher (as assessed by ambulatory blood pressure monitoring) underwent noninvasive imaging to ensure that their renal arteries were suitable for RDN.

A total of 136 patients were then randomly assigned to receive either ultrasound-based RDN or a sham procedure. Neither the patients nor the doctors they saw for follow-up visits knew who received RDN and who received the sham procedure. All patients continued to take the once-a-day combination pill during the 2-month follow-up period. The patients’ urine was tested to evaluate how well they followed their treatment with the three-medication pill during the study.

The primary efficacy endpoint was the change in daytime ambulatory systolic blood pressure from study entry to 2 months. The investigators also monitored major adverse events occurring within 30 days of the procedure, including death from any cause, kidney failure, blood clot, any complications involving the veins or arteries serving the kidneys that required treatment, or a severe increase in blood pressure.

Daytime ambulatory systolic blood pressure, 24-hour ambulatory systolic blood pressure, nighttime ambulatory systolic blood pressure, and systolic blood pressure measured in the doctor’s office were all significantly lower with RDN compared with the sham procedure. No differences in major adverse events were observed between the treatment arms.

The investigators will continue to follow the patients in the study for 3 years to assess the durability, safety, and ongoing benefit of the RDN procedure, advised Dr. Kirtane in the ACC announcement.