Clinical trial NCT06063941: High-concentration Small-volume Versus Low-concentration Large-volume Iodine Solution for Esophageal Chromoendoscopy
Official title: High-concentration Small-volume Versus Low-concentration Large-volume Iodine Solution for Esophageal Chromoendoscopy: a Multicenter, Randomized Equivalence Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Lugol chromoendoscopy
Adverse event
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
Collaborators: name: Ankang Central Hospital
name: The First Affiliated Hospital of ShiheziI University
name: Xi'an International Medical Center Hospital
name: Air Force 986 Hospital
First posted: 2023-10-03
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Visual analogue scale scores at 30 minutes after chromoendoscopy
timeFrame: 30 minute after endoscopy
Secondary outcomes:
measure: The color objective evaluation after chromoendoscopy
timeFrame: 2-3 minutes after spraying Lugol's iodine.
measure: The color subjective evaluation after chromoendoscopy
timeFrame: During endoscopy.
measure: Heart rate variability
timeFrame: 5 minute or 30 minute after endoscopy
measure: The incidence rate of the need for additional iodine solution spraying
timeFrame: During endoscopy.
measure: The dosage of additional iodine spraying
timeFrame: During endoscopy
measure: Visual analogue scale scores at 5 minutes after chromoendoscopy
timeFrame: 5 minute after endoscopy
measure: The incidence rate of esophageal spasms
timeFrame: During endoscopy
measure: The incidence rate of adverse incidents
timeFrame: Up to 48 hours after the endoscopy
measure: The incidence rate of upper abdominal discomfort or pain.
timeFrame: 5 minute or 30 minute after endoscopy
measure: Associated factors for visual analogue scale scores
timeFrame: Up to 48 hours after the endoscopy
Other outcomes:
Locations:
city: Ankang
country: China
facility: Ankang Central Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Xijing Hospital of Digestive Diseases
state: Shaanxi
city: Xi'an
country: China
facility: Air Force 986 Hospital
state: Shaanxi
city: Xian
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
city: Shihezi
country: China
facility: The First Affiliated Hospital of Shihezi University
state: Xinjiang
Study officials:
affiliation: Xijing Hospital of Digestive DIsease
name: Zhiguo Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Jin D, Wang J, Zhan Q, Huang K, Wang H, Zhang G, Xu Y, Yao J, Sun R, Huang Q, Ye F, Zhang G. The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial. Gastrointest Endosc. 2020 Sep;92(3):554-564. doi: 10.1016/j.gie.2019.11.028. Epub 2019 Nov 26.
citation: 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.
citation: Liu M, Zhou R, Guo C, Xu R, Liu A, Yang H, Li F, Duan L, Shen L, Wu Q, Liu Z, Liu F, Liu Y, Pan Y, Cai H, Weiss NS, He Z, Ke Y. Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus. Gastrointest Endosc. 2021 May;93(5):1065-1073.e3. doi: 10.1016/j.gie.2020.09.020. Epub 2020 Sep 18.
citation: Park JM, Seok Lee I, Young Kang J, Nyol Paik C, Kyung Cho Y, Woo Kim S, Choi MG, Chung IS. Acute esophageal and gastric injury: complication of Lugol's solution. Scand J Gastroenterol. 2007 Jan;42(1):135-7. doi: 10.1080/00365520600825141.
citation: Tsurumaru D, Utsunomiya T, Matsuura S, Komori M, Kawanami S, Ishibashi T, Honda H. Gastric mucosal changes caused by Lugol's iodine solution spray: endoscopic features of 64 cases on screening esophagogastroduodenoscopy. Gastroenterol Res Pract. 2010;2010:494195. doi: 10.1155/2010/494195. Epub 2010 Apr 12.
citation: Thuler FP, de Paulo GA, Ferrari AP. Chemical esophagitis after chromoendoscopy with Lugol's solution for esophageal cancer: case report. Gastrointest Endosc. 2004 Jun;59(7):925-6. doi: 10.1016/s0016-5107(04)00173-7. No abstract available.
citation: 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.