Corticosteroid Treatment in the Acute Phase of Caustic Ingestion Management (CORTICAU)

Corticosteroid Treatment in the Acute Phase of Caustic Ingestion Management for the Prevention of Refractory Stenosis of the Esophagus and Pharynx- The CORTICAU Study

The management of patients who have ingested a caustic product has changed since 2007. Whereas previously the lesion assessment and surgical indication were based on endoscopic data, the therapeutic algorithm is currently based solely on the results of a CT scan with contrast injection, performed 6 hours after ingestion. This examination makes it possible to reliably assess the viability of the esophageal and gastric walls and thus to indicate digestive resection. The therapeutic consequences of this new treatment are important because, by expanding the indications for conservative treatment after severe ingestion, it brings a significant gain in terms of survival, morbidity and functional outcome. In the absence of emergency digestive resection, however, the functional prognosis is often overshadowed by the formation of esophageal stenosis in the months following ingestion. Patients then require endoscopic dilation treatment. In the event of failure or impossibility of dilation, which defines refractory stenosis, esophageal reconstruction is necessary. In case of sequential pharyngeal stenosis following ingestion, esophageal and pharyngeal reconstruction is indicated as a first-line treatment, since these stenosis do not respond to endoscopic dilations. The expansion of the indications for conservative treatment after severe ingestion using CT scans has led to an increase in the incidence of after-effect stenosis.

We aim to develop a therapeutic approach that will prevent the development of refractory and pharyngeal esophageal stenosis. Indeed, there is currently no strategy that has proven effective in this regard in adults. The value of corticosteroid therapy for the prevention of caustic stenosis has only been evaluated in children and remains controversial.

The main objective is to evaluate the effect of early systemic corticosteroid therapy on the risk of refractory esophageal or pharyngeal stenosis within one year of ingestion of a caustic substance in a population of patients at high risk of stenosis, defined according to tomodensitometric criteria (grade IIb: severe lesions, absence of transparietal necrosis), and for whom there is no indication of urgent digestive resection.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Stenosis; Caustic Esophageal Injury; Pharyngeal Stenosis
• Intervention / Treatment: Drug: Methylprednisolone; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Helene CORTE; Phone Number: 01.42.49.49.49; Email: helene.corte@aphp.fr
• Study Contact Backup: Name: Marie-Quitterie PICAT; Phone Number: 01.42.49.97.42; Email: marie-quitterie.picat@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age greater than or equal to 18 years
• Recent caustic product ingestion (time between taking the product and initiating the evaluated treatment or placebo between 6 and 24 hours after ingestion)
• Predictive CT criteria for high-risk esophageal stenosis (grade IIb) in its most pathological part
• Written, signed consent (trusted person if necessary, in case of impossibility of collection)
• Beneficiary of a social security system

Exclusion Criteria:

• Indication of resection or surgical exploration in emergency
• History of caustic ingestion
• Corticosteroids taken at a dose greater than 20 mg prednisone within 7 days before randomization
• Contraindication to corticosteroid therapy:
• Any infectious condition that required antibiotic treatment within 7 days of randomization
• Any vaccine living within 7 days of randomization
• Hypersensitivity to one of the components
• Pregnancy in progress
• Breastfeeding in progress
• Co-intoxication involving vital prognosis and requiring, according to the patient's doctor, intensive care management
• Patient under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Methylprednisolone; Dose: 500mg/day for the first two days then 2mg/kg per day for three days. Dilution in 0.9% NaCl, 100 ml as a single slow intravenous administration over 60 minutes Total processing time of 5 days	Drug: Methylprednisolone; Dose: 500mg/day for the first two days then 2mg/kg per day for three days. Dilution in 0.9% NaCl, 100 ml as a single slow intravenous administration over 60 minutes Total processing time of 5 days; Other Names: Corticosteroid treatment
PLACEBO_COMPARATOR: Placebo (no corticosteroid treatment); NaCl 0.9%, 100ml per day as a single slow intravenous administration over 60 minutes for a total treatment duration of 5 days	Other: Placebo; NaCl 0.9%, 100ml per day as a single slow intravenous administration over 60 minutes for a total treatment duration of 5 days; Other Names: Control Arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indication for esophageal or pharyngeal surgical reconstruction	The primary outcome is the indication for esophageal or pharyngeal surgical reconstruction due to: The occurrence of one or more esophageal stenosis refractory to endoscopic dilation within 12 months of ingestion, as defined by:The need for more than 5 sessions of esophageal endoscopic dilationNon-expandable stenosis or esophageal obstruction;An esophageal perforation that occurs during dilation, which contraindicates the continuation of dilation.; The occurrence of pharyngeal stenosis, defined by the need to perform pharyngoplasty.	within 12 months post ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay in the occurrence of refractory stenosis or pharyngeal stenosis	Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis	at 1 month
Delay in the occurrence of refractory stenosis or pharyngeal stenosis	Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis	at 3 months
Delay in the occurrence of refractory stenosis or pharyngeal stenosis	Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis	at 6 months
Delay in the occurrence of refractory stenosis or pharyngeal stenosis	Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis	at 9 months
Delay in the occurrence of refractory esophagal stenosis or pharyngeal stenosis	Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis	at 12 months
Distance of the stenosis	Distance between the stenosis and the dental arches (cm)	at 1 month
Distance of the stenosis	Distance between the stenosis and the dental arches (cm)	at 3 months
Distance of the stenosis	Distance between the stenosis and the dental arches (cm)	at 6 months
Distance of the stenosis	Distance between the stenosis and the dental arches (cm)	at 9 months
Distance of the stenosis	Distance between the stenosis and the dental arches (cm)	at 12 months
Number of stenosis	Number of stenosis will be evaluated by endoscopy	at 1 month
Number of stenosis	Number of stenosis will be evaluated by endoscopy	at 3 months
Number of stenosis	Number of stenosis will be evaluated by endoscopy	at 6 months
Number of stenosis	Number of stenosis will be evaluated by endoscopy	at 9 months
Number of stenosis	Number of stenosis will be evaluated by endoscopy	at 12 months
Length of stenosis	Length of each stenosis will be evaluated by endoscopy	at 1 month
Length of stenosis	Length of each stenosis will be evaluated by endoscopy	at 3 months
Length of stenosis	Length of each stenosis will be evaluated by endoscopy	at 6 months
Length of stenosis	Length of each stenosis will be evaluated by endoscopy	at 9 months
Length of stenosis	Length of each stenosis will be evaluated by endoscopy	at 12 months
Estimated diameter of stenosis	Diameter of each stenosis will be evaluated by endoscopy	at 1 month
Estimated diameter of stenosis	Diameter of each stenosis will be evaluated by endoscopy	at 3 months
Estimated diameter of stenosis	Diameter of each stenosis will be evaluated by endoscopy	at 6 months
Estimated diameter of stenosis	Diameter of each stenosis will be evaluated by endoscopy	at 9 months
Estimated diameter of stenosis	Diameter of each stenosis will be evaluated by endoscopy	at 12 months
Endoluminal inflammation	Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe)	at 1 month
Endoluminal inflammation	Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe)	at 3 months
Endoluminal inflammation	Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe)	at 6 months
Endoluminal inflammation	Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe)	at 9 months
Endoluminal inflammation	Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe)	at 12 months
Number of dilation sessions	Number of dilation sessions evaluated by endoscopy	at 1 month
Number of dilation sessions	Number of dilation sessions evaluated by endoscopy	at 3 months
Number of dilation sessions	Number of dilation sessions evaluated by endoscopy	at 6 months
Number of dilation sessions	Number of dilation sessions evaluated by endoscopy	at 9 months
Number of dilation sessions	Number of dilation sessions evaluated by endoscopy	at 12 months
Intervals between iterative dilations	Time between endoscopic dilatations if necessary iterative dilation	at 1 month
Intervals between iterative dilations	Time between endoscopic dilatations if necessary iterative dilation	at 3 months
Intervals between iterative dilations	Time between endoscopic dilatations if necessary iterative dilation	at 6 months
Intervals between iterative dilations	Time between endoscopic dilatations if necessary iterative dilation	at 9 months
Intervals between iterative dilations	Time between endoscopic dilatations if necessary iterative dilation	at 12 months
Digestive perforations	Proportion of digestive perforations secondary to endoscopic dilation	at 1 month
Digestive perforations	Proportion of digestive perforations secondary to endoscopic dilation	at 3 months
Digestive perforations	Proportion of digestive perforations secondary to endoscopic dilation	at 6 months
Digestive perforations	Proportion of digestive perforations secondary to endoscopic dilation	at 9 months
Digestive perforations	Proportion of digestive perforations secondary to endoscopic dilation	at 12 months
Extent of pharyngeal stenosis	Laryngeal stenosis associated with pharyngeal stenosis	at 1 month
Extent of pharyngeal stenosis	Laryngeal stenosis associated with pharyngeal stenosis	at 3 months
Extent of pharyngeal stenosis	Laryngeal stenosis associated with pharyngeal stenosis	at 6 months
Extent of pharyngeal stenosis	Laryngeal stenosis associated with pharyngeal stenosis	at 9 months
Extent of pharyngeal stenosis	Laryngeal stenosis associated with pharyngeal stenosis	at 12 months
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at day 0
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at day 2
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at day 5
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at day 7
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at one month
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at 3 months
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at 6 months
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at 9 months
Proportion of unanticipated adverse reactions	Unanticipated adverse reactions will be defined by the occurrence of death,cardiac arrest whatever the cause,unplanned admission to intensive care unit (ICU) or extended stay > 24 ICU	at 12 months
Proportion of adverse reactions related to corticosteroid therapy	Adverse reactions related to corticosteroid therapy will be defined by the occurrence of infections needing antibiotic therapy or spontaneous digestive perforation or digestive bleeding or cardiac arrhythmias de novo or pulmonary edema requiring treatment (increased oxygen requirements and/or Diuretic and/or Vasodilator and/or non-invasive ventilation and/or invasive ventilation) or respiratory complications (High blood pressure requiring treatment - Metabolic alkalosis- Hypokalemia<3.0mmol/l - Delirium- Decompensation of a psychiatric pathology)	within 7 days
C-Reactive Protein (CRP)	Inflammation markers	at day 0
C-Reactive Protein (CRP)	Inflammation markers	at day 2
C-Reactive Protein (CRP)	Inflammation markers	at day 5
C-Reactive Protein (CRP)	Inflammation markers	at one month
interleukin-1 (IL1)	Inflammation markers	at day 0
interleukin-1 (IL1)	Inflammation markers	at day 2
interleukin-1 (IL1)	Inflammation markers	at day 5
interleukin-1 (IL1)	Inflammation markers	at one month
interleukin-6 (IL-6)	Inflammation markers	at day 0
interleukin-6 (IL-6)	Inflammation markers	at day 2
interleukin-6 (IL-6)	Inflammation markers	at day 5
interleukin-6 (IL-6)	Inflammation markers	at one month
Tumour Necrosis Factor alpha (TNF alpha)	Inflammation markers	at day 0
Tumour Necrosis Factor alpha (TNF alpha)	Inflammation markers	at day 2
Tumour Necrosis Factor alpha (TNF alpha)	Inflammation markers	at day 5
Tumour Necrosis Factor alpha (TNF alpha)	Inflammation markers	at one month
Tissue Growth Factor Beta (TGF beta)	Fibrosis markers	at day 0
Tissue Growth Factor Beta (TGF beta)	Fibrosis markers	at day 2
Tissue Growth Factor Beta (TGF beta)	Fibrosis markers	at day 5
Tissue Growth Factor Beta (TGF beta)	Fibrosis markers	at one month
Galectin 3	Fibrosis markers	at day 0
Galectin 3	Fibrosis markers	at day 2
Galectin 3	Fibrosis markers	at day 5
Galectin 3	Fibrosis markers	at one month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 15, 2019
• Primary Completion (ANTICIPATED): February 15, 2020
• Study Completion (ANTICIPATED): February 15, 2023

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (ACTUAL): November 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Esophageal Stenosis; Caustic; Pharyngeal Stenosis; Corticosteroid treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Pathological Conditions, Anatomical; Esophageal Diseases; Constriction, Pathologic; Esophageal Stenosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: P160803-J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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