Corticosteroid Treatment in the Acute Phase of Caustic Ingestion Management

Study Overview
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Brief Summary
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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.

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

Conditions
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Caustic Esophageal Injury, Esophageal Stenosis, Pharyngeal Stenosis

Intervention / Treatment
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* Drug: Methylprednisolone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective Phase II, Bayesian, single-blinded, monocentric, randomized, prospective clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylprednisolone<br>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<br>* 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<br>* Other names: Corticosteroid treatment;|
| Placebo Comparator: Placebo (no corticosteroid treatment)<br>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<br>* NaCl 0.9%, 100ml per day as a single slow intravenous administration over 60 minutes for a total treatment duration of 5 days<br>* Other names: Control Arm;|

What is the study measuring?
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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 dilation Non-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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caustic, Esophageal Stenosis, Pharyngeal Stenosis, Corticosteroid treatment