Safety, Acceptability and Efficacy of Noninvasive Transcutaneous-Autonomic Neuromodulation in Uncontrolled Hypertension.

BACKGROUND

Despite antihypertensive medications, ≈40% of patients with hypertension fail to achieve recommended blood pressure (BP) targets. Alternative device-based strategies are often expensive or invasive. We evaluated the safety, acceptability, and potential efficacy of a noninvasive transcutaneous autonomic neuromodulation (tAN) device.

METHODS

SCRATCH-HTN (Sham Controlled Randomized Trial Evaluating the Safety, Acceptability and Efficacy of Autonomic Neuromodulation using Transcutaneous Vagal Sensory Stimulation in Uncontrolled Hypertensive Patients) was a double-blind, sham-controlled, phase 2a trial enrolling patients with uncontrolled hypertension (mean daytime systolic BP [SBP] ≥135 mm Hg and diastolic BP ≥85 mm Hg) on 1 or more medications. Participants self-administered active tAN or sham treatment for 30 minutes daily for 14 days, then 10 weekly sessions. Primary end points were safety and acceptability. The primary efficacy end point was change in daytime ambulatory SBP from baseline to 3 months. Secondary end points included BP, heart rate, and quality of life at 1 and 3 months.

RESULTS

Sixty-three patients (mean age 47.2 years, 71.4% male, mean daytime BP 150/95 mm Hg) were randomized 2:1 to tAN or sham. tAN did not differ significantly from sham in daytime ambulatory SBP at 3 months (between-group difference, 2.35 mm Hg [95% CI, -4.37 to 9.07]; P=0.49) or 1 month (-1.01 mm Hg [-6.87 to 4.85]; P=0.73). Pre-specified adjusted analysis identified a significant interaction between treatment and baseline SBP (P interaction 0.003): participants with baseline SBP >160 mm Hg showed a greater response to tAN. No significant differences were observed for other secondary end points. tAN was safe and acceptable.

CONCLUSIONS

tAN is safe and well-tolerated in patients with hypertension. No significant BP-lowering effect was demonstrated, although a potential benefit in subgroups or a modest effect in a larger cohort cannot be excluded and warrants evaluation.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05179343. URL: XXX; Unique identifier: 14509154.