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Urinary Proteomics Combined With Home Blood Pressure Telemonitoring for Health Care Reform (UPRIGHT-HTM)

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ClinicalTrials.gov Identifier: NCT04299529
Recruitment Status : Not yet recruiting
First Posted : March 6, 2020
Last Update Posted : March 6, 2020
Sponsor:
Collaborator:
Alliance for the Promotion of Preventive Medicine
Information provided by (Responsible Party):
Jan A. Staessen, KU Leuven

Tracking Information
First Submitted Date  ICMJE March 2, 2020
First Posted Date  ICMJE March 6, 2020
Last Update Posted Date March 6, 2020
Estimated Study Start Date  ICMJE April 1, 2020
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2020)
  • Primary composite endpoint [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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.
  • Change in serum creatinine (mg/dl) [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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).
  • Change in eGFR (ml/min/1.73m2) [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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.
  • Progression of CKD [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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
  • Incidence of diabetic nephropathy [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    Microalbuminuria of 30 microgram per gram creatinine or more in two of three morning urine samples collected on three consecutive days.
  • Incidence of diabetic retinopathy [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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)
  • Incidence of hypertensive retinopathy [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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
  • Incidence of electrocardiographic LV hypertrophy [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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
  • Incidence of echocardiographic LV hypertrophy [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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.
  • Incidence of diastolic LV dysfunction [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    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).
  • Incidence of CV mortality [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    ICD10 codes I00-I99
  • Incidence of nonfatal myocardial infarction [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    ICD10 codes I21,I22
  • Incidence of nonfatal heart failure [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    ICD10 code I50
  • Incidence of nonfatal stroke [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    ICD10 codes I60-I63
  • Incidence of CKD [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years ]
    ICD10 codes N17, N18
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2020)
  • EQ-5D (scale ranging from 0 [worst possible] to 100 [best possible]) [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years. ]
    Quality of life will be assessed using the EQ-5D quality of life questionnaire (http://www.euroqol.org)
  • Health-economic analysis [ Time Frame: After a run-in period of 2 to 5 weeks to check the eligibility, patients will be randomized and followed up for 4 years. ]
    For health-economic evaluation, the EQ-5D patient-administered questionnaire (https://www.euroqol.org) is of particular importance, as Quality Adjusted Life Years (QALYs) can be generated from this simple instrument
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Urinary Proteomics Combined With Home Blood Pressure Telemonitoring for Health Care Reform
Official Title  ICMJE Urinary Proteomics Combined With Home Blood Pressure Telemonitoring for Health Care Reform: a Randomised Controlled Trial
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
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel group design
Masking: Single (Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Diagnostic
Condition  ICMJE
  • Protein Deregulation
  • Blood Pressure
  • Health Care Utilization
  • Cost Effectiveness
  • Patient Empowerment
Intervention  ICMJE Diagnostic Test: In-vitro urinary 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).
Study Arms  ICMJE
  • Experimental: HTM plus UPP
    Urinary proteomic profiling administered on top of home blood pressure telemonitoring and guideline-endorsed non-pharmacological and pharmacological management of risk factors
    Intervention: Diagnostic Test: In-vitro urinary diagnostic test
  • HTM alone
    Home blood pressure telemonitoring administered on top of non-pharmacological and pharmacological management of risk factors
    Intervention: Diagnostic Test: In-vitro urinary diagnostic test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 5, 2020)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2026
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jan A Staessen, MD, PhD +32 47 632 4928 jan.staessen@med.kuleuven.be
Contact: Zen-Yu Zhang, MD, PhD +32 16 34 7104 zhenyu.zhang@med.kuleuven.be
Listed Location Countries  ICMJE Belgium,   Denmark,   Germany,   Greece,   Nigeria,   Poland,   Slovenia,   South Africa,   Uruguay
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04299529
Other Study ID Numbers  ICMJE UPRIGHT-HTM, version 4.0
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: A motivated request for data transfer for scientific purposes should be addressed to Prof Jan A. Staessen
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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
Responsible Party Jan A. Staessen, KU Leuven
Study Sponsor  ICMJE KU Leuven
Collaborators  ICMJE Alliance for the Promotion of Preventive Medicine
Investigators  ICMJE
Principal Investigator: Lutgarde Thijs, MSc University of Leuven
PRS Account KU Leuven
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP