Urinary Proteomics Combined With Home Blood Pressure Telemonitoring for Health Care Reform

NCT04299529 | Not Yet Recruiting

• 1 other identifier: UPRIGHT-HTM, version 4.0
• Study Type: interventional
• Target: 1,000
• Locations: 9 countries
• Sites: 12

Brief Summary

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

Conditions

Protein Deregulation; Blood Pressure; Health Care Utilization; Cost Effectiveness; Patient Empowerment

Outcome Measures

Primary Outcomes (15)

• Primary composite endpoint

  The primary endpoint is a composite of intermediary and "hard" cardiovascular-renal endpoints. The "intermediate endpoints" are diabetic nephropathy, progression to a higher CKD stage, doubling of serum creatinine, an eGFR decrease by 30% or more or eGFR declining below 45 ml/min/1.73 m2, new-onset hypertensive or diabetic retinopathy, electrocardiographic or echocardiographic left ventricle hypertrophy, and diastolic left ventricular dysfunction. The "hard" composite cardiovascular endpoint includes cardiovascular mortality, and nonfatal myocardial infarction, nonfatal hospitalised heart failure, and nonfatal stroke, not including transient ischemic attack. The "hard" renal outcomes include macroalbuminuria, the need for renal-replacement therapy, and death to renal causes.

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Change in serum creatinine (mg/dl)

  The concentration of creatinine in serum, expressed in mg/dl, will be measured, using Jaffe's method with modifications () in certified laboratories applying isotope-dilution mass spectrometry for calibration (Clin Chem 2006; 52: 5-18).

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Change in eGFR (ml/min/1.73m2)

  eGFR will be derived from the serum creatinine concentration by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Ann Intern Med 2009; 150: 604-612) and expressed in ml/min/1.73 m2.

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Progression of CKD

  The National Kidney Foundation Kidney Disease Outcomes Quality Initiative guideline will be followed (Kidney Int Suppl 2013;3:1-150): eGFR ≥90, 60-89, 45-59, 30-44, 15-29 and \<15 mL/min/1.73 m2 for Stage 1, 2, 3A, 3B, 4 and 5, respectively

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of diabetic nephropathy

  Microalbuminuria of 30 microgram per gram creatinine or more in two of three morning urine samples collected on three consecutive days.

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of diabetic retinopathy

  Non-proliferative diabetic retinopathy (NPDR): early NPDR, at least one microaneurysm ; moderate NDPR, characterized by multiple microaneurysms, dot-and-blot hemorrhages, venous beading, and/or cotton wool spots; severe NPDR, diffuse intraretinal hemorrhages and microaneurysms in four quadrants, venous beading in two or more quadrants, or severe intraretinal microvascular abnormalities Proliferative diabetic retinopathy (PDR): fibrovascular proliferation extending beyond the internal limiting membrane; vitreous hemorrhage; retinal detachment, macular edema (https:// https://webeye.ophth.uiowa.edu/eyeforum/tutorials/Diabetic-Retinopathy-Med-Students/Classification.htm)

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of hypertensive retinopathy

  Grade 1: mild narrowing and tortuosity of the retinal arterioles; Grade 2: definite focal retinal arteriolar narrowing and arteriovenous nipping; Grade 3: retinal hemorrhages and cotton wool spots; Grade 4: papilledema

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of electrocardiographic LV hypertrophy

  The Sokolow-Lyon index is the sum of the S-wave in V1 and the R wave in V5 or V6, whichever is greater; the threshold value is 3.5 mV (PMID 31352838, 19015402, 28789616); in regularly calibrated ECGs, 1 mV is 10 mm along the vertical axis; The Cornell product is the sum of RaVL and RV5 with 6 mV added for women, multiplied by the QRS duration in milliseconds; the cut-off value is 2440 mV × ms (PMID 31352838, 19015402, 28789616); Increased R-wave in aVL: the threshold values is 1.1 mV; ST segment down sloping in V4-V6 with T-top inversion. Based on these criteria the investigators will classify patients as having or not having electrocariographic LV hypertrophy

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of echocardiographic LV hypertrophy

  Guidelines should be applied for acquisition and off-line analysis of the echocardiographic imaging studies (PMID 15452478, 19187853, 27037982); LV mass will be calculated using a formula validated by necropsy (PMID 2936235, 15452478); LVM = 0.8 × (1.04 × (EDD + IVS + LPW)3 - EDD)3) + 0.6; expressed in gram; LV mass will be indexed to body surface; the threshold values are ≥95/≥115 g/m2 in women/men.

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of diastolic LV dysfunction

  Diastolic LV dysfunction will be defined as an abnormally low age-specific transmitral E/A ratio, indicative of impaired relaxation, or a mildly-to-moderately elevated left ventricular filling pressure (E/e' \>8.5) with normal or decreased age-specific E/A ratio. The ejection fraction should be over 50% (Circ Heart Fail 2009;2: 105-112).

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of CV mortality

  ICD10 codes I00-I99

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of nonfatal myocardial infarction

  ICD10 codes I21,I22

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of nonfatal heart failure

  ICD10 code I50

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of nonfatal stroke

  ICD10 codes I60-I63

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

• Incidence of CKD

  ICD10 codes N17, N18

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years

Secondary Outcomes (2)

• EQ-5D (scale ranging from 0 [worst possible] to 100 [best possible])

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years.

• Health-economic analysis

  After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years.

Study Arms (2)

HTM plus UPP

EXPERIMENTAL

Urinary proteomic profiling administered on top of home blood pressure telemonitoring and guideline-endorsed non-pharmacological and pharmacological management of risk factors

Diagnostic Test: In-vitro urinary diagnostic test

HTM alone

OTHER

Home blood pressure telemonitoring administered on top of non-pharmacological and pharmacological management of risk factors

Diagnostic Test: In-vitro urinary diagnostic test

Interventions

In-vitro urinary diagnostic test DIAGNOSTIC_TEST

Urinary proteomic profiling (UPP) using established multidimensional urinary markers for progression to CKD (CKD273), left ventricular dysfunction (HF1 and HF2) and coronary heart disease (CAD238 and ACSP75) - in-vitro test certified in Germany and by extension in the EU (DE/CA09/0829/IVD/001, DE/CA09/0829/IVD/005).

HTM alone; HTM plus UPP

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• KU Leuven: lead
• Alliance for the Promotion of Preventive Medicine: collaborator

Study Sites (12)

European Kidney Health Aliance

Brussels, 1000, Belgium

Location

Diabetes Liga

Ghent, 9000, Belgium

Location

Alliance for the Promotion of Preventive Medicine

Mechelen, 2800, Belgium

Location

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

Mosaiques-Diagnoostics and Therapeutics AG

Hanover, D-30659, Germany

Location

Biomedical Research Foundation of the Academy of Athens

Athens, 115 27, Greece

Location

Department of Internal Medicine, Faculty of Clinical Sciences, College of Health Sciences, University of Abuja

Abuja, NCT Airport Road, Nigeria

Location

Department of Hypertension, Medical University of Gdańsk

Gdansk, 80-214, Poland

Location

First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College

Krakow, Poland

Location

Department of Internal Medicine, Division of Hypertension, University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Hypertension in Africa Research Team, Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University

Potchefstroom, 2520, South Africa

Location

Centro de Nefrología and Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República

Montevideo, 11600, Uruguay

Location

Related Publications (1)

• Chori BS, An DW, Martens DS, Yu YL, Gilis-Malinowska N, Abubakar SM, Ibrahim EA, Ajanya O, Abiodun OO, Anya T, Tobechukwu I, Isiguzo G, Cheng HM, Chen CH, Liao CT, Mokwatsi G, Stolarz-Skrzypek K, Wojciechowska W, Narkiewicz K, Rajzer M, Brguljan-Hitij J, Nawrot TS, Asayama K, Reyskens P, Mischak H, Odili AN, Staessen JA; UPRIGHT-HTM Investigators. Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report. J Clin Hypertens (Greenwich). 2023 Jun;25(6):521-533. doi: 10.1111/jch.14664. Epub 2023 May 6.

  PMID: 37147930 DERIVED

MeSH Terms

Conditions

Patient Acceptance of Health Care; Patient Participation

Condition Hierarchy (Ancestors)

Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Lutgarde Thijs, MSc

  University of Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan A Staessen, MD, PhD

CONTACT

+32 47 632 4928; jan.staessen@med.kuleuven.be

Zen-Yu Zhang, MD, PhD

CONTACT

+32 16 34 7104; zhenyu.zhang@med.kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Parallel group design

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 6, 2020
• Study Start: April 1, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 6, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Starting after completion of the trial for a duartion of 5 years
• Access Criteria: Approval by the Ethics Committee of the University Hospitals Leuven

Locations

DE (1); BE (3); SL (1); PL (2); NG (1); UR (1); DK (1); ZA (1); GR (1)