Clinical trial NCT06222866: Anticoagulation and Inflammation Monitoring in Patients After Heart and Vascular Interventions
Official title: Anticoagulation and Inflammation Monitoring in Patients After Heart and Vascular Interventions: Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Surgery
Vascular Surgery
Delirium
Hyperinflammatory Syndrome
Keywords: cardiac surgery
vascular surgery
Anticoagulation
Adverse Events
Monitoring
Delirium
Inflammation
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2024-01-25
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients needing cardiac or vascular surgery who receive anticoagulation

Brief 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events occurence
timeFrame: Patient follow-up of maximum 30 days
Secondary outcomes:
measure: ACT, aPTT, ROTEM, anti-factor Xa: Specific measured anticoagulation levels associated with adverse events
timeFrame: Patient follow-up of maximum 30 days
measure: Correlation of each anticoagulation monitoring test with another (ACT, aPTT, ROTEM, anti-F-Xa)
timeFrame: Patient follow-up of maximum 30 days
measure: Incidence of UFH-rebound and the need for protamine application
timeFrame: Patient follow-up of maximum 30 days
measure: Anticoagulation needs for patients receiving ECMO support and experiencing inflammation
timeFrame: Patient follow-up of maximum 30 days
measure: Association of significant inflammation with adverse events
timeFrame: Patient follow-up of maximum 30 days
measure: Incidence of ECMO support and delirium
timeFrame: Patient follow-up of maximum 30 days
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tirol
Study officials:
References: