Clinical trial NCT04143386: Prognostic Hemodynamic and Metabolic Profiles of Late Stage Lower Extremity Arterial Disease
Official title: Prognostic Hemodynamic and Metabolic Profiles of Late Stage Lower Extremity Arterial Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lower Extremity Arterial Disease (Fontaine Stages IIb-IV)
Keywords: lower extremity arterial disease
hemodynamics
arterial stiffness
metabolism
metabolomics
inflammation
oxidative stress
biomarkers
prognosis
Lead sponsor: University of Tartu
Sponsor class: OTHER
Collaborators: name: Estonian Science Foundation
name: Tartu University Hospital
First posted: 2019-10-29
Enrollment: 750
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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).

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of major adverse cardiovascular events, major adverse limb events and deaths
timeFrame: 5 years
Secondary outcomes:
measure: Number of fatal cardiovascular events
timeFrame: 5 years
measure: Number of non-fatal cardiovascular events
timeFrame: 5 years
measure: Number of LEAD-related major lower extremity amputations
timeFrame: 5 years
measure: Number of hospitalizations for angioplasty or bypass surgery for coronary or peripheral vessel disease
timeFrame: 5 years
measure: Number of deaths from all causes
timeFrame: 5 years
Other outcomes:
Locations:
city: Tartu
country: Estonia
facility: Tartu University Hospital
state: Tartumaa
Study officials:
affiliation: University of Tartu
name: Jaak Kals, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Tartu
name: Jaan Eha, MD, PhD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Mihkel Zilmer, dr. med.
role: STUDY_CHAIR
affiliation: University of Tartu
name: Kaido Paapstel, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Tartu
name: Kaspar Tootsi, MD, PhD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Karl Kuusik, MD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Tuljo Ööbik, MD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Riina Kaur
role: STUDY_CHAIR
References: