Comparison of Dexamethasone and N Acetylcysteine (NAC) Versus N Acetylcysteine (NAC) Alone in the Prevention of Post Embolization Syndrome in Patients With Hepatocellular Carcinoma Following Transarterial Chemoembolization.

Comparison of Dexamethasone and N Acetylcysteine (NAC) Versus N Acetylcysteine (NAC) Alone in the Prevention of Post Embolization Syndrome in Patients With Hepatocellular Carcinoma Following Transarterial Chemoembolization - Randomized Controlled Trial.

N-acetylcysteine (NAC), a glutathione precursor and potent antioxidant, is known as a liver protector. As a steroid preparation, dexamethasone is known to have efficient anti-inflammation and immunosuppression effects. N-acetyl cysteine and Dexamethasone's roles in preventing post-embolization syndrome following TACE have each been researched individually in the past. Up until now, no study has been done that has compared dexamethasone and NAC in post-embolization syndrome. With this study, we aim to study the efficacy of combining dexamethasone with N-acetyl cysteine in the prevention of post-embolization syndrome within 72 hours among patients who undergo transarterial chemoembolization for HCC.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: N Acetylcysteine; Drug: Dexamethasone; Other: Placebo

Detailed Description

Aim & Objectives Hypothesis: The combination of dexamethasone with NAC is superior to NAC alone in prevention of PES among patients who undergo TACE in HCC as both medications work differently to prevent PES.

AIM:- To study the efficacy of combining Dexamethasone to N acetyl cysteine in prevention of post embolization syndrome within 72 hours among patients who undergo transarterial chemoembolization for HCC.

Objective - PRIMARY Prevention of post embolisation syndrome within 72 hours.

SECONDARY

• Prevention of post embolisation decompensation at 2 weeks.
• Decrease in the duration of hospitalization.
• To study the adverse effects of NAC and steroids in patients who undergo transarterial chemoembolisation for HCC.

Methodology:

Study population:

• All patients undergoing TACE procedure
• Valid Consent
• Age 18-65 years

Study design:

Monocentric open label prospective randomized controlled study. The study will be conducted in Department of Hepatology, ILBS.

Sample size:

• Assuming that NAC prevents PES by 75% and addition of dexamethasone further prevents PES by 20 % (i.e combination of NAC and Dexamethasone prevents total 95%).
• Then with alpha as 5% and power 90 % .we need to enroll total 130 cases i.e 65 in each arm.
• Further assuming 10% drop out , it is decided to enroll 150 cases i.e. 75 in each arm.
• Allocation will be done randomly by block randomization method, taking block size as 10.

Monitoring and assessment: All the parameters of the objective and also noted any adverse effects.

Intervention: TACE.

STATISTICAL ANALYSIS:

The data will be entered in Microsoft excel and will be analyzed using SPSS version 22. The categorical data will be analyzed using Chi square/Fissure test. Exact test and continuous data will be compiled using t-test. Besides this the univariate and multivariate survival analysis will be carried out using Cox regression method. Kaplan-Meier technique will be applied for further analysis. P-value<0.05 will be considered as significant.

Adverse effects: allergic drug reaction.

Stopping rule: If patient decided to withdraw from study.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Phool Chand, MD; Phone Number: 01146300000; Email: phoolchand99@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Phool Chand, MD; Phone Number: 01146300000; Email: phoolchand99@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients undergoing TACE procedure
• Valid Consent
• Age 18-65 years

Exclusion Criteria:

• Child Pugh C, Child Pugh B > 8
• HCC patients with a curative therapy (Ablation, Resection or LT)
• ECOG Performance Status 3-4
• Pregnancy
• History of allergic reaction from NAC
• significant cardiopulmonary disease
• UGI bleed within last 28 days
• Recent surgery within last 28 days
• Documented febrile illness in last 1 weeks
• Uncontrolled Diabetes (FBS > 200, HBA1C > 8)
• Uncontrolled Hypertension (BP > 160/100)
• Structural kidney disease with eGFR < 60 ml/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC+Dexamethasone; NAC started at 12 hr prior to procedure - (150 mg/kg/hr for 1 hr followed by 12.5 mg/Kg/hr for 4 hr, then continuous infusion of 6.25 mg/h for 48 after the procedure. Dexamethasone 20 mg in 5 ml NS 1 hour prior to procedure and 8 mg in 5 ml NS at day 2, day 3. Placebo 5 ml NS 1 hr prior to procedure.	Drug: N Acetylcysteine; NAC started at 12 hr prior to procedure - (150 mg/kg/hr for 1 hr followed by 12.5 mg/Kg/hr for 4 hr, then continuous infusion of 6.25 mg/h for 48 after the procedure.; Drug: Dexamethasone; Dexamethasone 20 mg in 5 ml NS 1 hour prior to procedure and 8 mg in 5 ml NS at day 2, day 3. Placebo 5 ml NS 1 hr prior to procedure.
Active Comparator: NAC+Placebo; NAC started at 12 hr prior to procedure - (150 mg/kg/hr for 1 hr followed by 12.5 mg/Kg/hr for 4 hr, then continuous infusion of 6.25 mg/h for 48 after the procedure.	Drug: N Acetylcysteine; NAC started at 12 hr prior to procedure - (150 mg/kg/hr for 1 hr followed by 12.5 mg/Kg/hr for 4 hr, then continuous infusion of 6.25 mg/h for 48 after the procedure.; Other: Placebo; The placebo will be administered in the same way as the drug in the experimental group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of post-embolization syndrome	Prevention of Post-embolization syndrome , Defined base on South west oncology group (SWOG) toxic coding less than 2 score	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of post TACE decompensation at 4 weeks	Metric / Method of measurement : Post TACE decompensation defined as an increase in Child-Pugh score of more than two points or newly developed decompensating events, such as ascites, hepatic encephalopathy, or serum total bilirubin > 2 mg/dL.	4 weeks
Decrease in the duration of hospitalisation		4 weeks
Adverse events of Dexamethasone and NAC in patients undergoing transarterial chemoembolisation for HCC		2 weeks

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Dexamethasone; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: ILBS-HCC-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No