The Efficacy of N-acetylcysteine on Alleviating Symptom Caused by Lugol Chromoendoscopy

The Efficacy of N-acetylcysteine on Alleviating Symptom Caused by Lugol Chromoendoscopy: a Prospective, Non-inferiority, Randomized Controlled Trial

Lugol chromoendoscopy is essential in detecting and characterizing squamous cell carcinoma of esophagus. Esophageal irritating symptom has been reported as an common adverse event, which could be alleviated by sodium thiosulfate solutions. However, sodium thiosulfate was not widely available. N-acetylcysteine has been previously used as a mucolytic reagent, we propose that it may also be used to alleviate irritating symptoms caused by Lugo's chromoendoscopy. A prospective, non-inferior, randomized double-blind clinical trial was designed to study the efficacy of N-acetylcysteine solutions in relieving esophageal discomfort .

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: sodium thiosulfate solution; Drug: N-acetylcysteine solution

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital of Digestive Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients at risk of esophageal squamous cell cancer including those over 50 years old, or over 45 years old with family history of esophageal squamous cell cancer;
• Patients with suspected esophageal lesions by screening endoscopy;
• Patients requiring surveillance after endoscopic resection or radiotherapy for esophageal squamous cell cancer one year later。

Exclusion Criteria:

• Patients allergic to iodine or with hyperthyroidism;
• Patients with advanced esophageal cancer, esophageal varices, esophageal ulcer or other conditions inadvisable for Lugol chromoendoscopy;
• Patients with severe gastroesophageal reflux disease or reflux symptoms which may interfered with the outcome measures of current study;
• Patients with postoperative esophageal stenosis affecting endoscopic observation;
• Patients with serious comorbidities that cannot tolerate un-sedated gastroscopy;
• Patients who could not cooperate with the observation including patients with mental disorders, severe neurosis or dysgnosia;
• Patients undergoing sedation or general anesthesia during endoscopy.
• Patients who do not agree to sign informed consent forms or follow the trial requirement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: sodium thiosulfate solution arm; 20ml of 5% sodium thiosulfate solution were prepared with 1g sodium thiosulfate crystal dissolved in normal saline in a 20 ml syringe	Drug: sodium thiosulfate solution; use sodium thiosulfate solution to alleviate esophageal irritation caused by Lugol's chromoendoscopy
Experimental: N-acetylcysteine solution arm; 20ml of 3% N-acetylcysteine solution were prepared with one piece of N-acetylcysteine effervescent tablet （ net weight 0.6g ）dissolved in normal saline in a 20 ml syringe	Drug: N-acetylcysteine solution; use N-acetylcysteine solution to alleviate esophageal irritation caused by Lugol's chromoendoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Visual analogue scale change	Visual analogue scale change for esophageal irritation after Lugol chromoendoscopy	30 minute after endoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with symptom	The percentage of patients with symptom after Lugol chromoendoscopy for certain time	5 minute or 30 minute or 24 hour after endoscopy
Neutralization rate	Neutralizing effect for residual iodine in esophagus and stomach	During endoscopy
Heart rate variability	the percentage of heart rate change 5 min or 30 min compared to that Before endoscopy	5 minute or 30 minute after endoscopy
Severe discomfort rate	the percentage of patient with Visual analogue scale over 4	5 minute or 30 minute after endoscopy
exam time	the time of endoscopy from the beginning of spraying diluted Lugol's solution to end of endoscopy minus time required for biopsy.	during endoscopy

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases
• Investigators: Principal Investigator: Shaohua Zhu, Xijing Hospital of Digestive Disease

Publications and helpful links

General Publications

• Kondo H, Fukuda H, Ono H, Gotoda T, Saito D, Takahiro K, Shirao K, Yamaguchi H, Yoshida S. Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy. Gastrointest Endosc. 2001 Feb;53(2):199-202. doi: 10.1067/mge.2001.110730.
• Gotoda T, Kanzaki H, Okamoto Y, Obayashi Y, Baba Y, Hamada K, Sakae H, Abe M, Iwamuro M, Kawano S, Kawahara Y, Okada H. Tolerability and efficacy of the concentration of iodine solution during esophageal chromoendoscopy: a double-blind randomized controlled trial. Gastrointest Endosc. 2020 Apr;91(4):763-770. doi: 10.1016/j.gie.2019.10.022. Epub 2019 Oct 25.
• Guo Q, Fan X, Zhu S, Zhao X, Fang N, Guo M, Liu Z, Han Y. Comparing N-acetylcysteine with sodium thiosulfate for relieving symptoms caused by Lugol's iodine chromoendoscopy: a randomized, double-blind trial. Gastrointest Endosc. 2022 Feb;95(2):249-257. doi: 10.1016/j.gie.2021.07.025. Epub 2021 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: adverse event; lugol chromoendoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Anti-Bacterial Agents; Respiratory System Agents; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Free Radical Scavengers; Expectorants; Pharmaceutical Solutions; Acetylcysteine; N-monoacetylcystine; Sodium thiosulfate
• Other Study ID Numbers: KY20202056-F-1

Drug and device information, study documents

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