A Sham Controlled Randomised Trial evaluating the Safety, Acceptability and Efficacy of Autonomic neuromodulation using Trans-Cutaneous vagal sensory stimulation in uncontrolled Hypertensive patients: Rationale and study design of the SCRATCH-HTN Study

BackgroundDespite the broad availability of antihypertensive drugs, approximately 40% of hypertensive patients fail to achieve the recommended blood pressure (BP) levels and may require alternative treatment(s). Currently, renal denervation is the only proven non-pharmacological device-based alternative treatment available but is a costly hospital-based invasive procedure that is unlikely to be widely available. Transcutaneous autonomic neuromodulation (tAN), if safe, acceptable and efficacious, can offer a non-invasive, inexpensive, self-administered device-based innovative adjunct or alternative to pharmacological therapy. MethodsSCRATCH-HTN is a double-blind, sham-controlled trial, with 63 participants randomised on a 2:1 basis to receive either tAN or sham-tAN treatment. Hypertensive patients on medications were included if they had elevated systo-diastolic BPs on daytime ambulatory BP monitoring (ABPM) (systolic BP (SBP) of [&ge;]135 and <170 mmHg and mean daytime diastolic BP (DBP) of [&ge;]85 and < 115 mmHg). Participants were trained to self-administer tAN therapy for 30 minutes every day for first 14 days, and then once a week for 10 weeks. The primary endpoint was the change in daytime ambulatory SBP from baseline to 3 months. Secondary endpoints included the change in 24-hour ambulatory and office SBP and DBP, BP variability, heart rate variability, quality of life, and sleep quality from baseline to end-of-treatment. Other exploratory outcomes included evaluation of impact on functional exercise (6-minute walk test), structural and functional changes in the heart, cognitive function and central blood pressures. In a subgroup of patients detailed autonomic functional assessment was conducted at the start and end of the study. ConclusionThe SCRATCH-HTN trial is a phase 2a study testing the safety, acceptability, and potential efficacy of tAN treatment for improving blood pressure control in patients with elevated BP despite medication. It also explores tANs effects on sleep, exercise tolerance, heart rate variability, central BP, cardiac structure, and autonomic function. If effective, it could offer a transformative approach to hypertension management. Registrationclinicaltrials.gov (NCT05179343).