Anticoagulation and Inflammation Monitoring in Patients After Heart and Vascular Interventions (PAC-AIM)

Anticoagulation and Inflammation Monitoring in Patients After Heart and Vascular Interventions: Prospective Observational Study

The goal of this prospective observational study is to evaluate the most appropriate anticoagulation monitoring tool for unfractionated heparin (UFH), by comparison of different monitoring modalities in relation to adverse events occurrence (thrombosis/bleeding).

The main study questions are:

• What is the most appropriate anticoagulation monitoring tool (ACT, aPTT, viscoelastic tests (ROTEM), and anti-Xa) for UFH
• What is the incidence of adverse events associated with anticoagulation and inflammation after heart and vascular interventions
• Is there an association of available anticoagulation thresholds and monitoring tests with bleeding and/or thrombosis occurrence
• Is there an association of inflammation with delirium

Secondary study objectives include:

• Association of anticoagulation levels as measured by ACT, aPTT, viscoelastic tests (ROTEM), and anti-factor-Xa with adverse events
• Correlation of each anticoagulation monitoring test with the UFH anti-Xa measurement
• Correlation of each anticoagulation monitoring test with another (ACT, aPTT, ROTEM, anti-F-Xa) and the amount of blood loss post surgery
• The incidence of UFH-rebound effect and the need for protamine application
• Association of inflammation and increased / reduced need for anticoagulation titration
• Correlation of anticoagulation dosing with anticoagulation monitoring tests and adverse events
• The association of inflammation with adverse events
• The association and impact of inflammation on measured levels of anticoagulation with available tests
• Influence of anticoagulation on mortality
• Incidence of ECMO support
• Incidence of delirium (hypoactive and hyperactive) and correlation with vital (newly onset postoperative atrial fibrillation amongst others) and laboratory parameters, including, and pre-existing neurological disorders

Study Overview

• Status: Recruiting
• Conditions: Delirium; Heart Surgery; Vascular Surgery; Hyperinflammatory Syndrome
• Intervention / Treatment: Diagnostic test: Anticoagulation monitoring

Detailed Description

Patients undergoing major heart and vascular surgery are often in need of intraoperative and/or postoperative anticoagulation. To ensure the appropriate blood concentration of anticoagulants and reduce the risk of adverse events, anticoagulation monitoring is crucial. In contrast, due to contact of blood with artificial surfaces, some patients develop hyperinflammation which may increase the risk of thrombosis.

Patients undergoing heart surgery require full heparinization before the start of the heart-lung machine, which is later reversed using protamine. The levels of anticoagulation are intraoperatively monitored with activated clotting time (ACT). In the postoperative period, the monitoring of rest-heparinization or rebound effect is further performed. In certain cases, the addition of protamine is needed, based on the available monitoring tests. The postoperative monitoring of anticoagulation is usually performed using ACT and activated partial thromboplastin time (aPTT), and may be extended by other diagnostic methods, including viscoelastic tests. Moreover, to ensure the hemostatic capacity of the patient, monitoring of other parameters (platelet count, fibrinogen concentration, prothrombin time quick assay (PT), antithrombin level, etc.) may be included. Finally, in the case of patients receiving extracorporeal life support (ECMO), continuous anticoagulation is indicated, and its monitoring is of immense importance.

Furthermore, in the case of vascular surgery, patients require unfractionated heparin (UFH) intraoperatively, including postoperative continuous infusion.

The evidence on correlation and available monitoring tools is scarce and contradictory, usually based on retrospective analyses of patients´ data from medical charts. Additionally, the role of inflammation in the development of delirium is still unclear, and this association is a subject of debate.

Well-known consequences of postoperative delirium (POD) include poor functional outcome with increased morbidity and mortality, and increased healthcare costs due to institutionalization and rehospitalization. The incidence of POD after cardiac and vascular surgery remains between 13 and 52%. The current hypothesis on the pathophysiology of POD includes disruption of the blood-brain barrier allowing peripheral inflammation and mediators to cause neuro-inflammation. Neurotoxicity induced by a disbalance of pro- and anti-inflammatory mediators and oxidative stress might explain neuronal damage and neurotransmitter disbalance responsible for POD. To improve patients´ functional outcome and the financial burden of POD there is a growing interest in identifying predictive and diagnostic (bio-)markers. The neurofilament light chain (NfL) protein has shown promising results as a potential biomarker for POD. However, the literature on cardiac and vascular patients is limited.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Sasa Rajsic, MD, PhD; Phone Number: 004367763004447; Email: sasa.rajsic@tirol-kliniken.at

Study Locations

• Austria
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • Recruiting
      • Medical University Innsbruck
      • Contact: Sasa Rajsic, MD, PhD; Phone Number: 004367763004447; Email: sasa.rajsic@tirol-kliniken.at
      • Principal Investigator: Sasa Rajsic, MD, PhD
      • Sub-Investigator: Barbara Sinner, Prof. Dr.
      • Sub-Investigator: Axel Kleinsasser, Univ.Doz.Dr.
      • Sub-Investigator: Corinna Velik-Salchner, Priv.Doz.Dr.
      • Sub-Investigator: Benedikt Treml, Priv.Doz.Dr.
      • Sub-Investigator: Nicole Innerhofer, MD
      • Sub-Investigator: Christine Eckhardt, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients needing cardiac or vascular surgery who receive anticoagulation

Description

Inclusion Criteria:

• Age: > 17 years
• Informed written consent
• Scheduled for cardiac intervention where the use of UFH is expected (elective surgery)
• Scheduled for vascular intervention when the need for perioperative anticoagulation is expected (elective surgery)
• Patients receiving ECMO support

Exclusion Criteria:

• Patients that are known to be pregnant
• Known participation in other interventional clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients after cardiovascular surgery who received anticoagulation; The investigated population comprises all patients after cardiovascular surgery who received anticoagulation. Subgroup analyses based on the level of inflammation, delirium, anticoagulation, and others will be conducted.	Diagnostic test: Anticoagulation monitoring; Evaluation of different monitoring modalities to find the most appropriate anticoagulation monitoring tool for UFH therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events occurence	Occurence of adverse events associated with anticoagulation monitoring and hyperinflammation	Patient follow-up of maximum 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACT, aPTT, ROTEM, anti-factor Xa: Specific measured anticoagulation levels associated with adverse events	Correlation and thresholds associated with adverse events	Patient follow-up of maximum 30 days
Correlation of each anticoagulation monitoring test with another (ACT, aPTT, ROTEM, anti-F-Xa)	Correlation between various tests	Patient follow-up of maximum 30 days
Incidence of UFH-rebound and the need for protamine application	The rate of UFH-rebound	Patient follow-up of maximum 30 days
Anticoagulation needs for patients receiving ECMO support and experiencing inflammation	Anticoagulation range for patients with inflammation	Patient follow-up of maximum 30 days
Association of significant inflammation with adverse events	Impact of inflammation on adverse events occurence	Patient follow-up of maximum 30 days
Incidence of ECMO support and delirium	The rate of delirium, and the ECMO rate in patients after cardiovascular surgery	Patient follow-up of maximum 30 days

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; cardiac surgery; Monitoring; Anticoagulation; Adverse Events; Delirium; vascular surgery
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Inflammation
• Other Study ID Numbers: PAC-AIM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The decision will be made

Drug and device information, study documents

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