Deep Venous Thrombosis and Long Term Complications

Deep Venous Thrombosis and Risk of Long Term Complications in Acutely Admitted Patients

In this cohort study, the investigators will investigate the concentration of biomarkers, e.g., inflammatory, anti-inflammatory, immunological, senescent, biochemical ratio-calculations and blood cell type among first time lower extremity deep venous thrombosis patients with and without SARS-CoV-2 infection and long term complications with a 2-year follow-up.

Study Overview

• Status: Recruiting
• Conditions: DVT of Legs
• Intervention / Treatment: Diagnostic test: Blood sample and Ultrasound examination

Detailed Description

Venous thromboembolism (VTE) which is a common concept for deep venous thrombosis (DVT) and pulmonary embolus (PE) is the third most common cardiovascular disease after myocardial infarction and stroke. The incidence of deep venous thrombosis (DVT) increases exponentially with age and is highest in high-income countries compared to low-income countries. The pathophysiology of DVT is of multicomplex aetiology and there are multifactorial causes leading to the development of DVT. In the long term, patients with DVT can experience reduced thrombus resolution, recurrent thrombosis, and post thrombotic syndrome (PTS), where inflammation has a major impact.

The investigators hypothesis are:

i. There is an increased level of biomarkers at time of diagnosis among DVT patients who develop PTS compared to DVT patients who do not develop PTS

ii. There is an elevated level of the biomarkers: suPAR, D-dimer, inflammatory, anti-inflammatory, immunological, and aging markers at the time of diagnosis of DVT in patients with SARS-CoV-2 infection compared to DVT patients without SARS-CoV-2 infection.

iii. There is an increased incidence of late complications such as PTS among DVT patients with SARS-CoV-2 infection compared to DVT patients without SARS-CoV-2 infection

Purpose:

In this clinical prospective cohort study the investigators will investigate and characterize acutely admitted patients with deep venous thrombosis via inflammatory, anti-inflammatory, immunological and ageing biomarkers to gain a better understanding of options about prevention and treatment of long-term complications

Data collection:

Eligible patients will be included in the Emergency Department by the physician responsible for the treatment.

Variables:

The following variables will be collected at inclusion and 4 follow-up visits: information on demographics, biomarkers (blood samples and ultrasound scan), clinical data from the patient case report, self-reported information on risk factors, socioeconomic variables, quality of life, and pain. Moreover, register data on socioeconomic status, morbidity, physical health by e.g. Charlson score, mortality, hospital visits, and prescriptions will be retrieved after 2 years of follow-up.

Sample size:

To detect a difference in suPAR (0-24 months) and the association between suPAR and the risk of developing PTS (0-24 months) a total of 150 participants are needed in the study.

The collected data will be kept in accordance with the Data Protection Agency guidelines. The studies are carried out in accordance with the principles of the Helsinki Declaration.

• Study Type: Interventional
• Enrollment (Anticipated): 178
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ove Andersen, M.D., Ph.D.; Phone Number: 004529333262; Email: ove.andersen@regionh.dk
• Study Contact Backup: Name: Izzet Altintas, M.D.; Phone Number: 004531252292; Email: izzet.altintas@regionh.dk

Study Locations

• Denmark
  • Copenhagen
    • Hvidovre, Copenhagen, Denmark, 2650
      • Recruiting
      • Copenhagen University Hospital Hvidovre
      • Contact: Izzet Altintas, M.D.; Phone Number: +4531252292; Email: izzet.altintas@regionh.dk
      • Contact: Ove Andersen, M.D., Ph.D.; Phone Number: 004538623335; Email: ove.andersen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or above
• First time lower extremity DVT
• Hospitalized at the Emergency Department

Exclusion Criteria:

• Patients without a Danish social security number
• Terminal patients
• Patients who do not understand or speak Danish

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Biomarkers and long term complications in DVT patients; Patients with DVT will be enrolled in the study during their hospitalization at the ED. The enrolled patients will have 4 follow-up visits, 1) during the first 14 days after diagnosis, 2) after 3 months, 3) after 12 months and 4) 24 months after the time of diagnosis.

Diagnostic test: Blood sample and Ultrasound examination; The ultrasound examination is a non-invasive procedure with no risks, adverse reactions, or discomforts associated with the examination. The study blood samples are mostly obtained at the same time as clinical blood sample collection in order to avoid unnecessary complications. The inclusion and ultrasound examiniation is performed by the patient responsible physician at the Emergency Department. Blood samples during the study period are performed by trained study staff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
suPAR - baseline	suPAR level in first-time DVT patients at the time of diagnosis (baseline)	Baseline
Change in suPAR - 90 days	Change in suPAR level in first-time DVT patients from the time of diagnosis (baseline) to 90 days	90 days
Change in suPAR - 12 months	Change in suPAR level in first-time DVT patients from the time of diagnosis (baseline) to 12 months	12 months
Change in suPAR - 24 months	Change in suPAR level in first-time DVT patients from the time of diagnosis (baseline) to 24 months	24 months
Association of suPAR and PTS - baseline	Association of suPAR and development of PTS in DVT patients from the time of diagnosis (baseline)	Baseline
Association of suPAR and PTS - 90 days	Association of suPAR and development of PTS in DVT patients from the time of diagnosis and 90 days after diagnosis	90 days
Association of suPAR and PTS - 12 month	Association of suPAR and development of PTS in DVT patients from the time of diagnosis and 12 months after diagnosis	12 months
Association of suPAR and PTS - 24 month	Association of suPAR and development of PTS in DVT patients from the time of diagnosis and 24months after diagnosis	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers in DVT patients - baseline	Biomarkers concerning inflammatory, anti-inflammatory, immunological and aging/ senescent cells (IL-1β, IL-6, IL-10, IL-15, IL-18, Trombin, Fibrin/ Fibrinogen, GDF-8, GDF-15, COX2, PGE2, CD57, Cystatin C, NGAL, FGF-21, FGF-23, MICA, ULBP2, Klotho, p16INK4a, p21Cip1, asparagine endopeptidase, DPP4, KLRG1, DNA-methylering, U-PA, Vitronectin, PAI-1, Tissue Factor, histoner, kromatin and NETs) at baseline.	Baseline
Biomarkers in DVT patients - change over time 90 days	Change in biomarkers concerning inflammatory, anti-inflammatory, immunological and aging/ senescent cells (IL-1β, IL-6, IL-10, IL-15, IL-18, Trombin, Fibrin/ Fibrinogen, GDF-8, GDF-15, COX2, PGE2, CD57, Cystatin C, NGAL, FGF-21, FGF-23, MICA, ULBP2, Klotho, p16INK4a, p21Cip1, asparagine endopeptidase, DPP4, KLRG1, DNA-methylering, U-PA, Vitronectin, PAI-1, Tissue Factor, histoner, kromatin and NETs) from time of diagnosis (baseline) to 90 days after diagnosis.	90 days
Biomarkers in DVT patients - change over time 12 months	Change in biomarkers concerning inflammatory, anti-inflammatory, immunological and aging/ senescent cells (IL-1β, IL-6, IL-10, IL-15, IL-18, Trombin, Fibrin/ Fibrinogen, GDF-8, GDF-15, COX2, PGE2, CD57, Cystatin C, NGAL, FGF-21, FGF-23, MICA, ULBP2, Klotho, p16INK4a, p21Cip1, asparagine endopeptidase, DPP4, KLRG1, DNA-methylering, U-PA, Vitronectin, PAI-1, Tissue Factor, histoner, kromatin and NETs) from time of diagnosis (baseline) to 12 months after diagnosis.	12 months
Biomarkers in DVT patients - change over time 24 months	Change in biomarkers concerning inflammatory, anti-inflammatory, immunological and aging/ senescent cells (IL-1β, IL-6, IL-10, IL-15, IL-18, Trombin, Fibrin/ Fibrinogen, GDF-8, GDF-15, COX2, PGE2, CD57, Cystatin C, NGAL, FGF-21, FGF-23, MICA, ULBP2, Klotho, p16INK4a, p21Cip1, asparagine endopeptidase, DPP4, KLRG1, DNA-methylering, U-PA, Vitronectin, PAI-1, Tissue Factor, histoner, kromatin and NETs) from time of diagnosis (baseline) to 24 months after diagnosis.	24 months
PTS in DVT patients - 90 days	Development of PTS in DVT patients from the time of diagnosis (baseline) and up to 90 days after diagnosis.	90 days
PTS in DVT patients - 12 months	Development of PTS in DVT patients from the time of diagnosis (baseline) and up to 12 months after diagnosis.	12 months
PTS in DVT patients - 24 months	Development of PTS in DVT patients from the time of diagnosis (baseline) and up to 24 months after diagnosis.	24 months

Collaborators and Investigators

• Sponsor: Ove Andersen
• Investigators: Principal Investigator: Ove Andersen, M.D., Ph.D., Department of Clinical Research; Study Chair: Izzet Altintas, M.D., Department of Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Anticipated): March 9, 2026
• Study Completion (Anticipated): March 9, 2026

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: aging; inflammation; immune system; DVT; anti-inflammation; PTS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: H-21061004 / 85280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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