Key Points:
- Approximately 40% of hypertensive patients fail to achieve recommended blood pressure (BP) targets despite antihypertensive medication treatments. Transcutaneous autonomic neuromodulation (tAN), a non-invasive, self-administered device-based approach, was evaluated as a potential adjunct to pharmacotherapy.
- The SCRATCH-HTN trial enrolled 63 patients on an average of two antihypertensive medications who still had uncontrolled BP, randomized 2:1 to active tAN or sham treatment using the AffeX-CT device for 3 months.
- While tAN was safe, well-tolerated, and demonstrated excellent adherence, it did not significantly reduce daytime ambulatory systolic blood pressure (SBP) compared to sham at 3 months.
Despite the availability of multiple effective antihypertensive drug classes, blood pressure (BP) control remains a persistent public health challenge, with approximately 40% of hypertensive patients failing to reach recommended targets. Currently available non-pharmacological interventions, such as renal denervation, are costly, invasive, and difficult to scale. Transcutaneous autonomic neuromodulation (tAN) – a non-invasive, self-administered approach that modulates autonomic tone via vagal sensory stimulation – has emerged as a potentially scalable adjunct.
The Sham-Controlled Randomized Control Trial evaluating the Safety, Acceptability and Efficacy of Autonomic Neuromodulation using TransCutaneous vagal sensory stimulation in uncontrolled Hypertensive patients (SCRATCH-HTN) [NCT05179343 ] was a double-blind, sham-controlled, phase 2a trial. The study enrolled patients with uncontrolled hypertension (ambulatory daytime BP ≥135 / ≥85 mmhg with at least one antihypertensive agent). Participants were randomized 2:1 to active tAN or sham (inactive) treatment using the AffeX-CT device, which delivers sub-perception threshold electrical stimulation to the ear. The device was self-administered for a total of 3 months. Primary endpoints were safety and acceptability of the device and change in daytime ambulatory SBP
Sixty-three patients were randomized to tAN (n=41) or sham (n=22). The average age was 47.2 years, 71.4% were male, mean daytime BP was 150/95 mmHg, and median hypertension duration was 5 years. Adherence was excellent in both arms: the median proportion of days with self-administered therapy was 100% and median daily device use was 30 minutes in both groups. Over 3 months, daytime ambulatory SBP decreased by 3.15 mmHg in the tAN group and by 5.50 mmHg in the sham group which was not stiatistically significant in either unadjusted or adjusted analysis. No significant differences were observed in secondary outcomes including 24-hour ambulatory BP, office BP, BP variability, heart rate variability indices, sleep quality or 6-minute walk test distance. A prespecified subgroup analysis identified a significant interaction between treatment and baseline SBP: participants with a baseline SBP ≥160 mmHg demonstrated a meaningfully greater reduction in SBP with tAN compared to sham. No serious adverse device effects were reported in either arm.
Limitations of the trial include its modest sample size and pilot design, which was powered to detect efficacy signals rather than definitively establish treatment benefit. The larger-than-anticipated reduction in the sham arm further diminished statistical power. Additionally, antihypertensive medication changes occurred in a minority of participants, which may have introduced confounding.
Presenting at the American College of Cardiology Scientific Sessions on March 28, 2026, lead investigator Dr. Ajay Gupta concluded that “tAN is safe, acceptable, and well-tolerated in hypertensive patients,” but that “there is no significant difference in BP reduction on tAN versus sham treatment in this cohort of uncontrolled hypertensive patients.” He noted that a potentially meaningful treatment effect may exist in patients with significantly elevated blood pressures (SBP ≥160 mmHg), and called for future phenotype-enriched trials, as well as objective markers to define likely responders.