Prognostic Hemodynamic and Metabolic Profiles of Late Stage Lower Extremity Arterial Disease (PREDICTOR)

Late stage lower extremity arterial disease (LEAD) is known to be associated with hemodynamic and metabolic abnormalities and very poor long-term prognosis. The prognostic value of hemodynamic and metabolic profiling, however, is yet to be determined in this patient group.

Current study aims to identify novel prognostic biomarkers for better risk stratification of late stage LEAD patients. It also allows to determine associations between hemodynamic/arterial stiffness indices, low-molecular weight metabolites and other substances (e.g. mediators of inflammation and bone-mineral metabolism, cardiac and kidney injury biomarkers, microRNAs) thus providing potentially valuable insight into the pathogenic mechanisms of this disease.

Study Overview

• Status: Recruiting
• Conditions: Lower Extremity Arterial Disease (Fontaine Stages IIb-IV)

• Study Type: Observational
• Enrollment (Anticipated): 750

Contacts and Locations

• Study Contact: Name: Kaido Paapstel, MD, PhD; Phone Number: +372 731 8317; Email: kaido.paapstel@kliinikum.ee

Study Locations

• Estonia
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50406
      • Recruiting
      • Tartu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptomatic lower extremity arterial disease referred to Tartu University Hospital for revascularization (angioplasty/stenting or bypass surgery).

Description

Exclusion Criteria:

• Fontaine stage I-IIa;
• acute limb ischemia;
• age <35 or >85 years;
• fasting < 6 hours;
• time since the last use of tobacco products < 4 hours;
• body mass index ≥ 40 kg/m2
• blood pressure ≥ 180/120mmHg;
• unstable angina;
• atrial fibrillation at the time of presentation;
• myocardial infarction, stroke or TIA during the preceding 3 months;
• any revascularization during the preceding 1 month;
• severe heart failure (NYHA IV);
• clinically significant heart valve disease;
• severe physical disability (other than limb ischemia);
• acute infectious disease;
• active malignancy or chemotherapy or disease-free < 5 years;
• type 1 diabetes;
• uncompensated thyrotoxicosis/hypothyroidism or other clinically significant endocrine disorders;
• moderate to severe asthma (GINA 2016);
• severe chronic obstructive pulmonary disease (mMRC grade 3-4)
• acute (KDIGO 2012) or chronic renal disease (eGFR-EPI <30mL/min/1.73 m2);
• clinically significant acute or chronic liver disease;
• severe anemia (<80 g/L);
• clinically significant neuroinflammatory or neurodegenerative disease;
• active rheumatism;
• clinically significant connective tissue disease;
• alcoholism or drug abuse;
• psychotic disorders

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of major adverse cardiovascular events, major adverse limb events and deaths	A composite of any of the following events, as documented by patients' hospital or death records: nonfatal myocardial infarction or stroke; fatal myocardial infarction or stroke; hospitalization for angioplasty or bypass surgery for coronary or peripheral vessel disease; LEAD-related major lower extremity amputation; other cardiovascular deaths (cardiac arrest, lethal arrhythmia, heart failure, aortic dissection or rupture); non-cardiovascular deaths	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of fatal cardiovascular events	5 years
Number of non-fatal cardiovascular events	5 years
Number of LEAD-related major lower extremity amputations	5 years
Number of hospitalizations for angioplasty or bypass surgery for coronary or peripheral vessel disease	5 years
Number of deaths from all causes	5 years

Collaborators and Investigators

• Sponsor: University of Tartu
• Collaborators: Tartu University Hospital; Estonian Science Foundation
• Investigators: Study Chair: Jaan Eha, MD, PhD, University of Tartu; Study Chair: Mihkel Zilmer, dr. med., University of Tartu; Study Director: Kaido Paapstel, MD, PhD, University of Tartu; Study Chair: Kaspar Tootsi, MD, PhD, University of Tartu; Study Chair: Tuljo Ööbik, MD, University of Tartu; Study Chair: Riina Kaur, University of Tartu

Publications and helpful links

Helpful Links

• Endothelial Research Centre

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 4, 2019
• Primary Completion (ANTICIPATED): December 31, 2024
• Study Completion (ANTICIPATED): December 31, 2025

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (ACTUAL): October 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: biomarkers; prognosis; inflammation; hemodynamics; oxidative stress; metabolism; arterial stiffness; lower extremity arterial disease; metabolomics
• Other Study ID Numbers: 283T10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No