Anticoagulation and Inflammation Monitoring in Patients After Heart and Vascular Interventions

Delirium Clinical Trial

— PAC-AIM  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06222866
• Other study ID #: PAC-AIM
• Status: Not yet recruiting
• Start date: March 1, 2024
• Est. completion date: April 1, 2026

Study information

• Verified date: January 2024
• Source: Medical University Innsbruck
• Contact: Sasa Rajsic, MD, PhD
• Phone: 004367763004447
• Email: sasa.rajsic[@]tirol-kliniken.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: April 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Heart Surgery
• Inflammation
• Vascular Surgery

Intervention

Diagnostic Test:
• Anticoagulation monitoring
Evaluation of different monitoring modalities to find the most appropriate anticoagulation monitoring tool for UFH therapy

Locations

Country	Name	City	State
Austria	Medical University Innsbruck	Innsbruck	Tirol

Sponsors (1)

Lead Sponsor	Collaborator
Medical University Innsbruck

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events occurence	Occurence of adverse events associated with anticoagulation monitoring and hyperinflammation	Patient follow-up of maximum 30 days
Secondary	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
Secondary	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
Secondary	Incidence of UFH-rebound and the need for protamine application	The rate of UFH-rebound	Patient follow-up of maximum 30 days
Secondary	Anticoagulation needs for patients receiving ECMO support and experiencing inflammation	Anticoagulation range for patients with inflammation	Patient follow-up of maximum 30 days
Secondary	Association of significant inflammation with adverse events	Impact of inflammation on adverse events occurence	Patient follow-up of maximum 30 days
Secondary	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