Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.