Personalized ViscoElastic Testing-guided Bleeding Management In Liver Surgery, Neurosurgery and Obstetrics (VETILNO)

Personalized ViscoElastic Testing-guided Bleeding Management In Liver Surgery, Neurosurgery and Obstetrics - a Prospective Comparison of the Novel ClotPro With ROTEM and TEG

The ClotPro analyzer is a new generation viscoelastic analyzer for the in vitro assessment of blood coagulation. This study aims to assess the agreement of ClotPro 6.0, ROTEM delta, and TEG 6s in three distinct cohorts: i) patients with liver disease undergoing liver surgery, ii) pregnant women undergoing elective cesarean section, and iii) patients undergoing elective intracranial neurosurgery. Further coagulation tests will be performed (standard laboratory coagulation tests, thrombin and plasmin generation tests) in an exploratory fashion to compare them with viscoelastic test results. The obtained test results will not result in any diagnostic or therapeutic consequences for patients included in this study.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Hemorrhages; Postpartum Hemorrhage; Bleeding Disorder; Liver Transplant; Thrombelastography
• Intervention / Treatment: Diagnostic test: Viscoelastic testing

Detailed Description

The primary research question is therefore to compare various parameters of standard ClotPro measurements with corresponding ROTEM delta and TEG 6s parameters.

Additionally, this study aims to close the following clinically important knowledge gaps:

Do VET results mirror measurements obtained by more holistic, in-depth analyses of the hemostatic system that are currently not available in clinical practice, such as TGA-TM and PG?

Which of the three investigated VET devices offers the most rapid availability of diagnostic results?

Do VET results have a predictive ability for the occurrence of perioperative bleeding and/or thromboembolic events?

Do VET results depict sex-specific differences in perioperative coagulation management?

Furthermore, by including a large number of patients from three distinct patient cohorts, this study intends to examine whether cohort-specific reference ranges need to be established for ClotPro. Thereby, this study aims to provide the foundation for an evidence-based ClotPro-guided perioperative coagulation management algorithm, which could upscale current opportunities of personalizing perioperative coagulation management.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Nikolaus Hofmann, MD; Phone Number: 00436645379719; Email: nikolaus.hofmann@meduniwien.ac.at
• Study Contact Backup: Name: Carlo Martin, MD; Phone Number: 00436801349429; Email: carlo.martin@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Christoph Dibiasi, MD; Phone Number: 0043 1 40400 41660; Email: christoph.dibiasi@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will be comprised of three groups:

1. Patients with liver disease undergoing elective liver surgery defined as one of the following invasive procedures a) liver resection (anatomic or non-anatomic segmental resection, right or left hepatectomy, right or left extended hepatectomy) or b) orthotopic liver transplantation.
2. Pregnant women undergoing elective cesarean section.
3. Patients undergoing elective intracranial neurosurgery

Description

Inclusion Criteria:

1. Vulnerable patient cohorts

   • Patients undergoing elective liver surgery defined as one of the following invasive procedures:

     • Liver resection (anatomic or non-anatomic segmental resection, right or left hepatectomy, right or left extended hepatectomy),
     • Orthotopic liver transplantation,
   • Pregnant women undergoing an elective caesarean section, and
   • Patients undergoing an elective intracranial neurosurgery.
2. Written informed consent

Exclusion Criteria:

none

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with functional liver disease undergoing liver surgery; This group consists of patients with liver disease undergoing elective liver surgery defined as one of the following invasive procedures a) liver resection (anatomic or non-anatomic segmental resection, right or left hepatectomy, right or left extended hepatectomy) or b) orthotopic liver transplantation.	Diagnostic test: Viscoelastic testing; viscoelasting testing refers to a global hemostatic assay,that quantifies the viscoelastic properties of citrated whole blood
neurosurgical patients undergoing intracranial procedures; This group consists of patients who undergo elective neurosurgery e.g. tumor resection, aneurysm clipping or other intracranial procedures.	Diagnostic test: Viscoelastic testing; viscoelasting testing refers to a global hemostatic assay,that quantifies the viscoelastic properties of citrated whole blood
pregnant women undergoing cesarean section; This group consists of pregnant women undergoing elective cesarean section.	Diagnostic test: Viscoelastic testing; viscoelasting testing refers to a global hemostatic assay,that quantifies the viscoelastic properties of citrated whole blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Limits of agreement viscoelastic test parameters	Calculate limits of agreement between the following corresponding viscoelastic test parameters: EX-test- clotting time vs. EXTEM-clotting time vs. citrated rapid TEG r time; EX-test- maxium clot firmness vs. EXTEM-maximum clot firmness vs. citrated rapid TEG-maximum amplitude; FIB-test-clotting time vs. FIBTEM-clotting time vs. citrated functional fibrinogen r time; FIB-test-maxium clot firmness vs. FIBTEM-maxium clot firmness vs. citrated functional fibrinogen-maximal amplitude	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In depth hemostatic assessment: Viscoelastic tests (VET) & thrombin generation assay (with thrombmodulin)	Correlation between the following viscoelastic test parameters and thrombin generation (TG) measurements: - Ex-test clotting time, citrated rapid TEG r time and the ratio of endogenous thrombin potential derived by TG assay using thrombomodulin	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
In depth hemostatic assessment: Viscoelastic tests (VET) & standard laboratory coagulation tests (SLT)	Correlation between the following VET parameters and SLT measurements: EX-test clotting time and citrated rapid TEG r time vs. prothrombin time and; FIB-test maximum clot firmness, citrated functional fibrinogen-maximal amplitude and citrated functional fibrinoge- functional level of fibrinogen vs. Clauss fibrinogen.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
In depth hemostatic assessment: Viscoelastic tests & plasmin generation (PG)	Correlation between the viscoelastic test parameters TPA-lysis time and TPA-maximal lysis with the endogenous plasmin potential derived by plasmin generation measurements.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Patient cohort-specific reference ranges	This anaylsis aims to investigate whether there is a need for cohort-specific reference ranges for ClotPro by assessing the distributional differences of ClotPro results between three patient cohorts (patients undergoing liver surgery, pregnant women undergoing elective cesarean section, patients undergoing an elective intracranial neurosurgery)	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Useability	To evaluate the clinical useability of the three viscoelastic test devices by assessing differences in time from starting sample processing until each device reports the following parameters: clot formation (CT / R) and clot firmness (MCF / MA)	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Predictability of clinical outcome: blood products	To assess wether baseline clot formation (CT / R) and clot firmness (MCF / MA) measurements for the extrinsic VET coagulation assays (EX-test, EXTEM, and CRT; FIB-test, FIBTEM, and CFF) correlate with the amount of blood product consumption.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Predictability of clinical outcomes: hemorrhage	To examine whether end of surgery clot formation (CT / R) and clot firmness (MCF / MA) measurements derived by viscoelastic test assays (EX-test, EXTEM, and CRT; FIB-test, FIBTEM, and CFF) correlate with hemorrhage defined by cCT imaging in patients undergoing intracranial neurosurgery.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Predictability of clinical outcomes: ocurrence of BIMS (Bleeding Independently associated with Mortality after noncardiac Surgery) or need for surgical bleeding control	To examine wether end of surgery clot formation (CT / R) and clot firmness (MCF / MA) measurements for the viscoelastic test assays (EX-test, EXTEM, and CRT; FIB-test, FIBTEM, and CFF) correlate with the occurrence of i) BIMS, ii) the need for interventional radiologic procedures to stop bleeding within the surgical site, or iii) the need for revision in the operating room within the first 30 postoperative days.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)
Predictability of clinical outcomes: thromboembolism	To examine whether a combination of baseline and end of surgery clot formation (CT / R) and clot firmness (MCF / MA) measurements for the viscelastic test assays (EX-test, EXTEM, and CRT; FIB-test, FIBTEM, and CFF) correlate with the occurrence of i) DVT (deep venous thrombosis), ii) PE (pulmonary embolism), ii) PVT (portal vein thrombosis) within the first 30 postoperative days.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24) Edit
Coagulational differences based on biological sex	In this analysis, differences in the coagulational profile as assessed by viscoelastic tests, standard laboratory coagulation tests, thrombin generation assays (with thrombomodulin) and plasmin generation measurements will be compared between subjects of female or male sex.	Baseline (immediately after induction of general anaesthesia / prior to regional anesthesia); end of the surgery / intervention (assessed up to 1h); Day 1: 1. postoperative day (assessed within 24h) ; Day 3: 3. postoperative day (assessed within 24)

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Synapse - Research Institute Maastricht
• Investigators: Principal Investigator: Johannes Gratz, PhD MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: September 27, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Viscoelastic testing; personalized bleeding management
• Additional Relevant MeSH Terms: Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Hematologic Diseases; Hemorrhagic Disorders; Puerperal Disorders; Uterine Hemorrhage; Postpartum Hemorrhage; Hemorrhage; Hemostatic Disorders; Blood Coagulation Disorders; Intracranial Hemorrhages
• Other Study ID Numbers: 1622/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No