Caustic Esophageal Injury, Esophageal Stenosis, Pharyngeal Stenosis
Conditions
Keywords
Caustic, Esophageal Stenosis, Pharyngeal Stenosis, Corticosteroid treatment
Brief summary
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.
Interventions
DRUGMethylprednisolone
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
OTHERPlacebo
NaCl 0.9%, 100ml per day as a single slow intravenous administration over 60 minutes for a total treatment duration of 5 days
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
single-blinded trial
Intervention model description
Prospective Phase II, Bayesian, single-blinded, monocentric, randomized, prospective clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Indication for esophageal or pharyngeal surgical reconstruction | within 12 months post ingestion | The primary outcome is the indication for esophageal or pharyngeal surgical reconstruction due to: 1. 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. 2. The occurrence of pharyngeal stenosis, defined by the need to perform pharyngoplasty. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Galectin 3 | at day 0 | Fibrosis markers |
| Delay in the occurrence of refractory stenosis or pharyngeal stenosis | at 1 month | Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis |
| Delay in the occurrence of refractory esophagal stenosis or pharyngeal stenosis | at 12 months | Time between inclusion and occurrence of refractory stenosis or pharyngeal stenosis |
| Distance of the stenosis | at 1 month | Distance between the stenosis and the dental arches (cm) |
| Number of stenosis | at 1 month | Number of stenosis will be evaluated by endoscopy |
| Length of stenosis | at 1 month | Length of each stenosis will be evaluated by endoscopy |
| Estimated diameter of stenosis | at 1 month | Diameter of each stenosis will be evaluated by endoscopy |
| Endoluminal inflammation | at 1 month | Importance of endoluminal inflammation during endoscopy performed for dilation (minimal, moderate, or severe) |
| Number of dilation sessions | at 1 month | Number of dilation sessions evaluated by endoscopy |
| Tissue Growth Factor Beta (TGF beta) | at day 0 | Fibrosis markers |
| Digestive perforations | at 1 month | Proportion of digestive perforations secondary to endoscopic dilation |
| Extent of pharyngeal stenosis | at 1 month | Laryngeal stenosis associated with pharyngeal stenosis |
| Proportion of unanticipated adverse reactions | at day 0 | 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 |
| Tumour Necrosis Factor alpha (TNF alpha) | at day 0 | Inflammation markers |
| Proportion of adverse reactions related to corticosteroid therapy | within 7 days | 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) |
| C-Reactive Protein (CRP) | at day 0 | Inflammation markers |
| interleukin-1 (IL1) | at day 0 | Inflammation markers |
| interleukin-6 (IL-6) | at day 0 | Inflammation markers |
| Intervals between iterative dilations | at 1 month | Time between endoscopic dilatations if necessary iterative dilation |
Contacts
Primary ContactHelene CORTE
Backup ContactMarie-Quitterie PICAT
Outcome results
None listed