High-concentration Small-volume Versus Low-concentration Large-volume Iodine Solution for Esophageal Chromoendoscopy

Study Overview
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Brief Summary
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This clinical trial aims to test the participants' tolerance for different concentration iodine solutions during esophageal chromoendoscopy. The main question it aims to answer is: Under the same iodine dosage, do the participants have the same tolerance for 1% and 5% iodine solutions? Participants will be asked to score based on pain and discomfort and describe symptoms and corresponding location at 5 minutes (only for unanesthetized participants) and 30 minutes after chromoendoscopy.

Detailed Description
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Lugol's iodine chromoendoscopy is the commonly used method for detecting and diagnosing esophageal squamous cell carcinoma. However, iodine can induce mucosal irritation and has been commonly associated with adverse retrosternal symptoms, including retrosternal pain and/or heartburn. The existing research shows that spraying iodine solution neutralizers (Sodium thiosulfate solution, N-acetylcysteine, and vitamin C solution) after esophageal iodine chromoendoscopy can alleviate patient discomfort. However, a recent study has shown that excessive iodine concentration or excessive dosage of iodine can still increase patient discomfort even under spraying an iodine solution neutralizer. It is currently unclear whether the factors affecting patient tolerance are the iodine solution concentration or the total dosage of iodine used. Therefore, the multicenter randomized controlled trial will compare the patient's tolerance for the 1% and 5% iodine solutions under the same iodine dosage conditions. The trial will help determine the specific reasons influencing patient tolerance. Participants will be asked to score based on pain and discomfort and describe symptoms and corresponding location at 5 minutes (only for unanesthetized participants) and 30 minutes after chromoendoscopy.

Official Title
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High-concentration Small-volume Versus Low-concentration Large-volume Iodine Solution for Esophageal Chromoendoscopy: a Multicenter, Randomized Equivalence Trial

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: 1% Lugol's iodine solution
* Drug: 5% Lugol's iodine solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing esophageal Lugol's iodine chromoendoscopy. Age ≥ 18 Exclusion Criteria: Patients allergic to iodine or with hyperthyroidism; Patients with 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 who could not cooperate with the observation and data collection including patients with mental disorders, severe neurosis, dysgnosia or communication disorder; Patients with advanced-stage tumors; Patients after upper gastrointestinal surgery; Patients who do not agree to sign informed consent forms or follow the trial requirement.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1% iodine solution arm<br>Esophageal chromoendoscopy will be performed with a 15 ml volume of 1% Lugol iodine solution. | Drug: 1% Lugol's iodine solution<br>* 1% Lugol iodine solution was sprayed from the esophagogastric junction towards a location approximately 20 cm away from the upper incisors in the cervical esophagus.<br>|
| Experimental: 5% iodine solution arm<br>Esophageal chromoendoscopy will be performed with a 3 ml volume of 5% iodine stock solution. | Drug: 5% Lugol's iodine solution<br>* Before chromoendoscopy, a 20 ml syringe was employed to draw 3 ml of 5% iodine stock solution and 17 ml air. When staining, the iodine was quickly expelled through the endoscope's working channel at 20 cm of the esophagus from the incisor. An iodine mist was created because of the rapid spurt of the iodine solution and air, which prompts even distribution of the iodine solution on the esophageal wall. The lower segments of the esophageal wall were stained with the remaining iodine solution in the working channel by repeatedly spraying the air/iodine mixture using the syringe, resulting in consistent and uniform staining for the whole esophagus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue scale scores at 30 minutes after chromoendoscopy | According to the visual analogue scale, participants will be asked to score based on pain or discomfort 30 minutes after chromoendoscopy. | 30 minute after endoscopy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The color objective evaluation after chromoendoscopy | After spraying Lugol's iodine, the esophageal mucosa displaying a homogeneous dark brown staining was classified as normal, while faded or unstained lesions larger than 0.5 cm were deemed potential high-grade intraepithelial neoplasia or mucosal cancer. The Lugol's unstained lesions were further evaluated for the presence of the pink-color sign and photographed 2-3 minutes after Lugol's iodine staining. The images were also taken at 30 cm distal to the incisors at 2-3 minutes after Lugol's iodine staining if no lesion was found. The images were retrospectively analyzed and scored for an objective evaluation based on the L* a* b* (L* = light/dark; a* = red/green; b* = yellow/blue) color values in the CIELAB color space system. | 2-3 minutes after spraying Lugol's iodine. | 
| The color subjective evaluation after chromoendoscopy | The endoscopist will be asked to complete a questionnaire survey immediately after chromoendoscopy. The questionnaire asked the endoscopist to rate the staining effect as good (The color concentration is sufficient and the color retention time is adequate) or poor (The color concentration is insufficient and/or the color retention time is inadequate). | During endoscopy. | 
| Heart rate variability | The percentage of heart rate change 5 min (only for unanesthetized participants) or 30 min compared to that before endoscopy. | 5 minute or 30 minute after endoscopy | 
| The incidence rate of the need for additional iodine solution spraying | When the endoscopist believes that insufficient esophageal iodine staining affects the detection or diagnosis of lesions, they can spray additional iodine solution. The incidence rate of the need for additional iodine solution spraying of the two groups will be compared. | During endoscopy. | 
| The dosage of additional iodine spraying | When the endoscopist believes that insufficient esophageal iodine staining affects the detection or diagnosis of lesions, they can spray additional iodine solution. The dosage of additional iodine spraying of the two groups will be compared. | During endoscopy | 
| Visual analogue scale scores at 5 minutes after chromoendoscopy | According to the visual analogue scale, participants without sedation or general anesthesia will be asked to score based on pain or discomfort 5 minutes after chromoendoscopy. | 5 minute after endoscopy | 
| The incidence rate of esophageal spasms | The incidence rate of esophageal spasms of the two groups will be compared. | During endoscopy | 
| The incidence rate of adverse incidents | The incidence rate of adverse incidents of the two groups will be compared. | Up to 48 hours after the endoscopy | 
| The incidence rate of upper abdominal discomfort or pain. | Participants will be asked to describe retrosternal discomfort symptoms and corresponding location at 5 minutes (only for unanesthetized participants)) and 30 minutes after chromoendoscopy. The incidence rate of upper abdominal discomfort or pain will be compared between the two groups. | 5 minute or 30 minute after endoscopy | 
| Associated factors for visual analogue scale scores | Visual analogue scale scores may be influenced by other factors. Univariable analysis will first be used to identify potential factors that influenced visual analogue scale scores. All possible factors will then be included in multivariable analysis. | Up to 48 hours after the endoscopy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lugol chromoendoscopy, Adverse event