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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorIuliu Hatieganu University of Medicine and Pharmacy

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

patients with a hepatocellular carcinoma suitable for RFA

tumor measuring up to 3 cm in diameter

ASA I, II, or III

Disqualifiers

candidates for surgery

chronic immunosuppressive medication

contraindications to any of the study medications

patients with psychiatric disorders

Trial design

Design model

Parallel

Treatments tested in this trial

  • Sedation using combination of Propofol and Fentanyl.

    Drug

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

  • 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)

Treatment groups

100 Participants
are divided into 2 treatment groups
Group A: Propofol and fentanyl sedationActive comparator 1 intervention
Group B: Propofol plus fentanyl plus lidocaineExperimental treatment 1 intervention

Trial outcomes

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.

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

Secondary outcomes

1

Change in Neutrophil-to-Lymphocyte Ratio (NLR)

Calculated as the ratio of absolute neutrophil count divided by the absolute lymphocyte count, obtained from a standard automated complete blood count (CBC).

Time frame
Pre-procedure (prior to sedation) and 24 hours post-procedure.
2

Change in Serum C-Reactive Protein (CRP) Concentration

Evaluation of the acute-phase inflammatory response measured via standard high-sensitivity serum C-reactive protein laboratory assays.

Time frame
Pre-procedure (prior to sedation) and 24 hours post-procedure.
3

12-Month Survival Rate

The percentage of patients alive at 12 months post-procedure. Survival status will be verified via clinical database records, in-person clinical follow-up, or telephone contact.

Time frame
From the day of the RFA procedure up to 12 months post-procedure.
4

12-Month Disease-Free Survival Rate

The percentage of patients alive without clinical or radiological evidence of local tumor recurrence or distant metastasis. Follow-up oncological status will be confirmed via contrast-enhanced computed tomography (CT), Contrast echocardiography or magnetic resonance imaging (MRI).

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

Other outcomes

1

12-Month Local Recurrence Rate

The percentage of patients presenting with new neoplastic activity or active tumor growth at the margin of, or within, the original completely ablated target lesion, confirmed via contrast-enhanced imaging (CT, Contrast echocardiography or MRI)

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

Sponsors and contacts

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