Protocol

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 spreading with epidemic proportions 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 (NCT04299529) is an investigator-initiated randomised clinical trial with a patient-centred design, for the first time, comparing HTM (Omron HEM-9210T) combined with 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. All patients will engage in HTM and will have their UPP determined on a single urine sample at enrolment. The trial will run in Europe, sub-Saharan Africa and South America. 

Eligible patients, aged 55-75 years old, are asymptomatic, but have five or more CKD- or DVD-related risk factors, preferably including hypertension, type‑2 diabetes mellitus, or both. 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, cardiac arrhythmias, 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.  In two arms of the trial, both patients and caregivers will have full access to the HTM data. In the experimental group, caregivers and patients will be informed about their UPP risk profile shortly after randomisation, but in the control group, only when a patient leaves randomised follow-up or at the completion of the trial. 

The underlying hypothesis is that knowledge of the UPP risk profile will be an extra motivation for patients and caregivers to be adherent and pro-active in personalised risk factor management.  The trial will run for 5 years with patients being recruited during the first year.  Assuming an annual drop-out rate of 2.5%, a 4-year primary endpoint rate of 20% and a 30% risk reduction in the experimental group, requires 1146 patients to be randomised in a 1:1 proportion with the two-sided a‑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 could lead to redesigning the clinical workflow, putting greater emphasis on preventing rather than curing established disease. 

Link to the UPRIGHT-HTM protocol article

 

 

UPRIGHT-HTM design 

The run-in period lasts from 2 to 5 weeks.  

Abbreviations: eCRF, electronic report forms completed by investigators; EP, absence (-)/incidence (+) of the components of the primary composite endpoint during the run-in/follow-up periods, respectively; IC, written informed consent; pINF, patients received the UPRIGHT-HTM information sheet and were familiarised with operating the blood pressure monitoring devices; pQ, patient-administered questionnaires, R, randomisation after stratification for centre and sex; S, initial screening; UPP, urinary proteomic profiling.

 

 

 

The OMRON HEM-9210T passed validation (https://medaval.ie/device/omron-hem-9210t).

 

 

 

Protocol article

The UPRIGHT-HTM protocol article has been published in Blood Pressure.  

Thijs L, Asayama K, Maestre GE, Hansen TW, Buysse L, Wei, DM, Melgarejo JD, Brgulian-Hitij J, Cheng HM, de Souza F, Gilis-Malinowski N, Kawecka-Jaszcz K, Mels C, Mokwatsi G, Muxfeldt ES, Narkiewicz K, Odili AN, Raizer M, Schutte AE, Stolarz-Skrzypek K, Tsai YW, Vanassche T, Van Holder R, Zhang ZY, Verhamme P, Kruger R, Mischak H, Staessen JA, the UPRIGHT-HTM Investigators, Coordinating, Logistic, Recruiting and Urinary Proteomics Centers, Advisors.  Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol.  Blood Pressure 2021; 30: 269-281
21-Thijs (Blood Pressure) (link to full text)

 

UPRIGHT-HTM in Abuja, Nigeria

After having obtained ethical approval, the Abuja team, led by Prof Augustine Odili, started screening and on 29 October 2021 had 25 patients randomized in UPRIGHT-HTM.