The Impact of Anaesthesia and Sedation on Inflammation and NETosis in Hepatocellular Carcinoma Ablation

NCT07657897 | Recruiting DMC

• 1 other identifier: 212/07.11.2024
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

According to recent literature, liver disease causes approximately 2 million deaths annually; 1 million are attributed to the complications of cirrhosis, while the remaining deaths are caused by hepatocellular carcinoma (HCC). The latter currently ranks 16th among the leading causes of death worldwide. Current research focuses on investigating novel therapeutic modalities, optimizing surgical and anesthetic practices, and identifying biological biomarkers to predict disease progression and severity. In this study, we address radiofrequency ablation (RFA) with the goal of improving periprocedural prognosis, recurrence rates, and overall survival. Specifically, we will quantify the expression of NETosis, a relatively novel biomarker with potential therapeutic and prognostic value in HCC progression. NETosis is a regulated form of cell death through which granulocytes release decondensed chromatin and various proteases into the extracellular space, forming a web-like meshwork known as neutrophil extracellular traps (NETs). These structures are actively involved in hepatic tumorigenesis by promoting tumor growth and metastasis. Recent clinical data reveal that NETs play a key role in: Local tumor progression The incidence of hepatic metastasis Direct modulation of the immune response Hepatic ischemia-reperfusion injury Several recent studies demonstrate that the in vivo blockade of NETosis reduces tumor recurrence, mitigates the pro-inflammatory state, and serves as a valuable prognostic indicator in advanced liver disease \[2,3,4\]. To suppress NETosis expression and ultimately lower recurrence rates, our protocol evaluates the intraprocedural administration of 1% lidocaine followed by a continuous postoperative intravenous lidocaine infusion.

Conditions

Hepato Cellular Carcinoma (HCC); Sedation and Analgesia; Ablation Techniques

Outcome Measures

Primary Outcomes (1)

• Change in Serum Citrullinated Histone H3 (H3Cit) Concentration

  To evaluate the effect of intraprocedural lidocaine on neutrophil extracellular trap (NET) formation, measured as the change in serum H3Cit concentration (ng/ml). Quantitative analysis of H3Cit will be performed using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit.

  Baseline (at the initiation of sedation) and 24 hours following the completion of the radiofrequency ablation (RFA) procedure.

Secondary Outcomes (4)

• Change in Neutrophil-to-Lymphocyte Ratio (NLR)

  Pre-procedure (prior to sedation) and 24 hours post-procedure.

• Change in Serum C-Reactive Protein (CRP) Concentration

  Pre-procedure (prior to sedation) and 24 hours post-procedure.

• 12-Month Survival Rate

  From the day of the RFA procedure up to 12 months post-procedure.

• 12-Month Disease-Free Survival Rate

  From the day of the RFA procedure up to 12 months.

Other Outcomes (1)

• 12-Month Local Recurrence Rate

  From the day of the primary RFA procedure up to 12 months.

Study Arms (2)

Propofol and fentanyl sedation

ACTIVE COMPARATOR

This group receives procedural sedation and analgesia acording to ASA guidlines with propofol and fentanyl alone.

Drug: Sedation using combination of Propofol and Fentanyl.

Propofol plus fentanyl plus lidocaine

EXPERIMENTAL

This group receives a procedural sedation and analgesia with propofol and fentanyl, combined with a 1.5 mg/kg slow bolus of lidocaine followed by an intravenous lidocaine infusion of 1 mg/kg/h for 24 hours (PF-L group).

Drug: Sedation using combination of Propofol and Fentanyl and lidocaine

Interventions

Sedation using combination of Propofol and Fentanyl. DRUG

Group 2 received PSA with propofol and fentanyl alone (PF group).

Also known as: Sedation using combination of propofol, fentanyl and lidocaine infusion

Propofol and fentanyl sedation

Sedation using combination of Propofol and Fentanyl and lidocaine DRUG

Group 1 received a procedural sedation and analgesia (PSA) with propofol and fentanyl, combined with a 1.5 mg/kg slow bolus of lidocaine followed by an intravenous lidocaine infusion of 1 mg/kg/h for 24 hours (PF-L group)

Propofol plus fentanyl plus lidocaine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with a hepatocellular carcinoma suitable for RFA
• tumor measuring up to 3 cm in diameter
• ASA I, II, or III

You may not qualify if:

• candidates for surgery
• chronic immunosuppressive medication
• contraindications to any of the study medications
• patients with psychiatric disorders
• autoimmune disorders
• corticosteroid-dependent bronchial asthma
• congenital or acquired coagulation disorders
• HIV-positive patients
• pregnant women
• antiarrhythmic therapy

Sponsors & Collaborators

• Iuliu Hatieganu University of Medicine and Pharmacy: lead

Study Sites (1)

"Prof. Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania

Cluj-Napoca, Cluj, 400394, Romania

RECRUITING

Related Publications (9)

• Foo I, Macfarlane AJR, Srivastava D, Bhaskar A, Barker H, Knaggs R, Eipe N, Smith AF. The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety. Anaesthesia. 2021 Feb;76(2):238-250. doi: 10.1111/anae.15270. Epub 2020 Nov 3.

  PMID: 33141959 RESULT

• Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer. 2014 Mar;14(3):199-208. doi: 10.1038/nrc3672.

  PMID: 24561446 RESULT

• Wee IJY, Moe FNN, Sultana R, Ang RWT, Quek PPS, Goh BKP, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, Koh YX, Mack POP, Ooi LLPJ, Tan EK, Teo JY, Kam JH, Chua JSS, Ng AWY, Goh JSQ, Chow PKH. Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System. J Hepatocell Carcinoma. 2022 Aug 17;9:839-851. doi: 10.2147/JHC.S370212. eCollection 2022.

  PMID: 35999856 RESULT

• Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010 Feb;30(1):61-74. doi: 10.1055/s-0030-1247133. Epub 2010 Feb 19.

  PMID: 20175034 RESULT

• McBrien M, Thomas ML. Unilateral renal dysplasia in the adult. Br J Urol. 1971 Aug;43(4):387-90. doi: 10.1111/j.1464-410x.1971.tb12057.x. No abstract available.

  PMID: 5095567 RESULT

• Facciorusso A. Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma: Current state of the art. World J Gastroenterol. 2018 Jan 14;24(2):161-169. doi: 10.3748/wjg.v24.i2.161.

  PMID: 29375202 RESULT

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 RESULT

• Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol. 2018 Feb;18(2):134-147. doi: 10.1038/nri.2017.105. Epub 2017 Oct 9.

  PMID: 28990587 RESULT

• Itoh Y, Yamada M. Apolipoprotein E and the neuropathology of dementia. N Engl J Med. 1996 Feb 29;334(9):599-600. doi: 10.1056/NEJM199602293340913. No abstract available.

  PMID: 8569837 RESULT

MeSH Terms

Conditions

Agnosia

Interventions

Fentanyl; Lidocaine

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant professor

Study Record Dates

• First Submitted: June 13, 2026
• First Posted: June 18, 2026
• Study Start: November 12, 2024
• Primary Completion: March 31, 2026
• Study Completion (Estimated): November 12, 2026
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1)