UPRIGHT-HTM will compare risk stratification, treatment efficiency and health economic outcomes of a diagnostic approach based on home blood pressure telemonitoring combined with urinary proteomic profiling with home blood pressure telemonitoring alone

Hypertension is by far the dominant reversible risk factor dwarfing most others in the pathogenesis of chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD), two archetypes of chronic age-related diseases, which are rampant in ageing societies in epidemiological transition. Home blood pressure telemonitoring (HTM) is a recommended approach in the diagnosis and management of hypertension. Urinary peptidomic profiling (UPP) holds great promise in individualising prevention and treatment of CKD and DVD and associated complications, such as coronary heart disease. Making use of these modern technologies, UPRIGHT-HTM is an investigator-initiated randomised clinical trial with a patient-centred design, for the first time, comparing HTM combined UPP (experimental group) to HTM alone (control group) in risk profiling and as guide to starting or intensifying management of risk factors to prevent established disease. The trial will run in Europe, sub-Saharan Africa and South America. Eligible patients, aged 55-75 years old, are asymptomatic, but have three or more CKD- or DVD-related risk factors, preferably including hypertension, type 2 diabetes mellitus, or both, and do have internet skills. The primary endpoint consists of a composite of new-onset intermediate endpoints (microalbuminuria, progression of CKD, diabetic or hypertensive retinopathy, electrocardiographic or echocardiographic left ventricular hypertrophy or DVD and hard outcomes (cardiovascular mortality and non-fatal complications, including myocardial infarction, heart failure and stroke). Secondary objectives are demonstrating that combining HTM with UPP is feasible and cost-effective in a multicultural context, defining the molecular signatures of early CKD and DVD, and with help of stakeholders educating and empowering patients. Assuming an accrual time of 1 year, a median follow-up of 4 years, a 10% dropout rate, a 20% risk of the primary endpoint in the control group and 30% risk reduction in the experimental group, requires 1000 patients to be randomised in a 1:1 proportion with the two-sided alpha level and power set 0.05 and 0.80, respectively. The expected outcome is proving the superiority in terms of efficiency and cost-effectiveness of HTM combined with UPP vs HTM alone, which should lead to redesigning the clinical workflow, putting greater emphasis on preventing rather than curing established disease.

Inclusion Criteria:

• Patients must have at least three additional guideline-defined risk factors, preferably including hypertension, type 2 diabetes mellitus (T2DM), or both;
• Patients should be willing patients to engage for the duration of the study in home blood pressure telemonitoring (1 reading per day);
• Patients must have an email address and internet access via smartphone, tablet, or laptop or desktop computer;
• Patients should comply with the study protocol during the run-in phase.

Exclusion Criteria:

• Type 1 diabetes mellitus;
• Absence of a practicable echocardiographic window;
• Previous or concurrent severe cardiovascular or non-cardiovascular disease;
• Cancer within 5 years of enrolment;
• Suspected substance abuse;
• Psychiatric illness;
• Use of nephrotoxic drugs;
• Particpation in another clinical study.

A motivated request for data transfer for scientific purposes should be addressed to Prof Jan A. Staessen

Starting after completion of the trial for a duartion of 5 years

Approval by the Ethics Committee of the University Hospitals Leuven

Caregivers will know the group to which their patients were randomly assigned. In the two groups, both patients and caregivers will have full access to the HTM data. In both treatment groups, caregivers will be informed about the UPP risk profile. However, in the experimental group, patients will be informed about their UPP risk profile shortly after randomisation and in the control group, only when they leave randomised follow-up or at the completion of the trial. The central study coordinating team will remain blinded to the primary endpoint and all of its components until completion of the trial and until all datasets have been cleaned and frozen for the final analysis.