Intralesional Steroid Injection Versus Oral Prednisolone in Prevention of Esophageal Stricture

Prospective, Randomized Trial of Intralesional Steroid Injection Versus Oral Prednisolone in Prevention of Esophageal Stricture After Endoscopic Submucosal Dissection

Endoscopic resection of superficial esophageal neoplasms is already a reality and presents important advantages when compared to esophagectomy as fewer complications and better quality of life. However, extensive resections can lead to difficult-to-manage stenoses. There are several therapies available in order to prevent this stenosis but, to date, there is no definition of the gold standard.

The objective of this study was to compare the use of intralesional steroid injection versus oral prednisolone after endoscopic submucosal dissection and to evaluate the stenosis rate, number of dilations to resolve the stenosis and complications.

Study Overview

• Status: Unknown
• Conditions: Esophageal Stenosis
• Intervention / Treatment: Drug: Local steroid - triamcinolone acetonide; Drug: Oral steroid - predonisolone

Detailed Description

Endoscopic resection of superficial esophageal neoplasms is widely used as an alternative to esophagectomy, since it is less invasive, besides presenting good clinical results. Compared with esophagectomy, patients submitted to endoscopic resection present shorter hospitalization time, lower incidence of complications and better quality of life in the long term.

However, repair of esophageal ulcer, caused by endoscopic resection, which occupies three quarters or more of the circumference of the organ, can result in the formation of stenosis.

In the past, there was no consensus on the use of preventive therapies for esophageal stenosis after extensive ESD. However, Oliveira et al recently demonstrated through systematic review and meta-analysis that the use of these therapies reduces the rate of stenosis (40% on average), decreased the number of dilations to resolve the stenosis (8 sessions less ), Without altering the number of complications.

Theoretically, corticosteroids are the most appropriate choice due to their mechanism of action, modulating wound healing by preventing inflammation, by reducing prolyl hydroxylase, which helps reduce collagen production.

However, treatment with corticosteroids, especially at high oral doses, can cause several adverse effects, such as immunosuppression, diabetes, psychiatric disorders, osteoporosis, optic lesion and peptic ulcer. Thus, the use of local corticosteroid injection could minimize these side effects. However, local injection implies risks of bleeding and perforation, and is of limited use in patients receiving anticoagulant or antiplatelet therapy.

The objective of this study was to compare the local corticosteroid injection and the use of oral corticosteroids to prevent stenosis after extensive submucosal endoscopic resection of superficial esophageal carcinoma, in relation to the stenosis rate, number of dilations necessary to resolve the stenosis and frequency of complications.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fauze Maluf-Filho, PhD; Phone Number: 55 11 99191-9014; Email: fauze.maluf@terra.com.br
• Study Contact Backup: Name: Joel F Oliveira, MD; Phone Number: 55 11 96382-0289; Email: jfoliveira1@gmail.com

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Instituto do Cancer do Estado de Sao Paulo - ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of superficial esophageal neoplasm submitted to submucosal endoscopic resection greater than 3/4 of the organ circumference;
• Absence of lymph node or distant metastases, evaluated through echoendoscopy, CT and PET-CT;
• Signed informed consent form

Exclusion Criteria:

• Presence of invasive esophageal neoplasia
• Hepatical cirrhosis
• Diabetes mellitus with fasting glycemia above 200mg%
• Use of corticosteroids in the 30 days prior to ESD
• INR> 1.5
• Platelet count less than 50,000
• Active gastrointestinal ulcer
• Severe psychiatric illness
• Glaucoma
• History of allergy or hypersensitivity to corticosteroids or proton pump inhibitor

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: Local steroid-triamcinolone acetonide; Local steroid (triamcinolone acetonide) injection to the ulcer immediately after ESD. Total amount of injected triamcinolone is 100 mg.	Drug: Local steroid - triamcinolone acetonide; (triamcinolone acetonide)
Active Comparator: Oral steroid-predonisolone; (predonisolone) administration three days after ESD. Predonisolone is administered over 8 weeks, started at 30 mg/day and tapered 30, 30, 25, 25, 20, 15, 10 and 5 every 7 days, totaling 8 weeks of treatment.	Drug: Oral steroid - predonisolone; (predonisolone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Stenosis rate	Stenosis to the passage of the standard endoscopic (9.8 mm)	12 weeks
Late Stenosis rate	Stenosis to the passage of the standard endoscopic (9.8 mm)	24 weeks
Early resistance rate	Resistance to the passage of the standard endoscopic (9.8 mm)	12 weeks
Late resistance rate	Resistance to the passage of the standard endoscopic (9.8 mm)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of dilations to solve the stenosis	Number of endoscopic dilations (Savary or balloon)	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Complications related to the procedure and preventive therapy.	24 weeks

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Anticipated): March 21, 2021
• Study Completion (Anticipated): June 21, 2021

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: ESD; esophageal stricture; steroid injection; endoscopy submucosal dissection; esophageal stenosis; oral prednisolone
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Pathological Conditions, Anatomical; Esophageal Diseases; Constriction, Pathologic; Esophageal Stenosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: NP888/2016

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
• product manufactured in and exported from the U.S.: No