Chemical adherence testing-guided intervention versus standard of care in patients with hypertension who are non-adherent to antihypertensive treatment in the UK (OUTREACH): a multicentre, randomised controlled trial.

Background: Biochemical urine analysis by liquid chromatography-mass spectrometry analysis (ie, chemical adherence testing [CAT]) is an objective method of detecting non-adherence to antihypertensive treatment. We aimed to assess whether an intervention based on providing non-adherent patients with hypertension with information on their urine analysis results combined with a discussion of the main reasons for non-adherence (CAT-guided intervention) would lead to a cost-effective improvement in adherence, blood pressure, and urinary excretion of albumin. Methods: OUTREACH was a multicentre, randomised controlled trial in 12 UK secondary or tertiary outpatient centres and primary care services. We recruited non-pregnant patients with hypertension who were older than 18 years and were on at least two antihypertensive medications. Participants who were non-adherent to antihypertensive treatment based on the results of their first urine CAT were randomly assigned (1:1) either to the intervention (discussion of the results of the urine CAT; group A) or standard of care (group B) after visit 2. The sequence of randomisation was computer-generated through an automated randomisation service (Sealed Envelope), which used minimisation as a method of allocation based on recruitment site, baseline systolic blood pressure, age, sex, number of antihypertensive medications prescribed at visit 1, the improvement in biochemical adherence to antihypertensive treatment between visits 1 and 2, and a random element to ensure the unpredictability of the assignment. The primary outcome was the mean clinic systolic blood pressure measured at visit 4. All analyses were based on the intention-to-treat principle. The trial was registered with ClinicalTrials.gov (NCT03293147) and is completed. Findings: Between Feb 4, 2019, and Feb 1, 2023, 879 patients were assessed for eligibility, 748 of whom were excluded after visit 1; 720 because they were either adherent or had unconfirmed adherence status on urine CAT. 70 adherent individuals were retained on the study for masking purposes but were not a part of the two-arm randomised component of the study. 130 non-adherent patients included in the study were randomly assigned to the intervention group (A; n=65) or the standard of care group (B; n=65). 71 (55%) participants were male and 59 (45%) were female; 57 (44%) were White, 22 (17%) were Asian or Asian British, 49 (38%) were Black, African, Caribbean, or Black British, and two (2%) were other ethnicities. The median follow-up after the intervention to visit 4 was 2·8 months (IQR 2·2-4·3). Mean clinic systolic blood pressure at visit 4 was 150·9 mm Hg (SD 24·7) in 56 participants in group A and 151·1 mm Hg (24·4) in 55 participants in group B (adjusted mean difference -5·1 mm Hg [95% CI -12·7 to 2·5]; p=0·19). 33 adverse events were reported (11 in group A and 22 in group B). 12 serious adverse events were recorded during the trial, occurring in five (8%) of 65 participants in group A and five (8%) of 65 participants in group B (two participants in group B had two serious adverse events each). Interpretation: CAT-guided intervention did not show a significant effect on clinic systolic blood pressure, but the study was underpowered. Larger studies are required to better understand the effect of urine CAT-guided interventions on blood pressure. Funding: British Heart Foundation, National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, and Omron.