Clinical trial NCT03760354: Corticosteroid Treatment in the Acute Phase of Caustic Ingestion Management
Official title: Corticosteroid Treatment in the Acute Phase of Caustic Ingestion Management for the Prevention of Refractory Stenosis of the Esophagus and Pharynx- The CORTICAU Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Caustic Esophageal Injury
Esophageal Stenosis
Pharyngeal Stenosis
Keywords: Caustic
Esophageal Stenosis
Pharyngeal Stenosis
Corticosteroid treatment
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-11-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective Phase II, Bayesian, single-blinded, monocentric, randomized, prospective clinical trial
Primary purpose: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Indication for esophageal or pharyngeal surgical reconstruction
timeFrame: within 12 months post ingestion
Secondary outcomes:
measure: Delay in the occurrence of refractory stenosis or pharyngeal stenosis
timeFrame: at 1 month
measure: Delay in the occurrence of refractory stenosis or pharyngeal stenosis
timeFrame: at 3 months
measure: Delay in the occurrence of refractory stenosis or pharyngeal stenosis
timeFrame: at 6 months
measure: Delay in the occurrence of refractory stenosis or pharyngeal stenosis
timeFrame: at 9 months
measure: Delay in the occurrence of refractory esophagal stenosis or pharyngeal stenosis
timeFrame: at 12 months
measure: Distance of the stenosis
timeFrame: at 1 month
measure: Distance of the stenosis
timeFrame: at 3 months
measure: Distance of the stenosis
timeFrame: at 6 months
measure: Distance of the stenosis
timeFrame: at 9 months
measure: Distance of the stenosis
timeFrame: at 12 months
measure: Number of stenosis
timeFrame: at 1 month
measure: Number of stenosis
timeFrame: at 3 months
measure: Number of stenosis
timeFrame: at 6 months
measure: Number of stenosis
timeFrame: at 9 months
measure: Number of stenosis
timeFrame: at 12 months
measure: Length of stenosis
timeFrame: at 1 month
measure: Length of stenosis
timeFrame: at 3 months
measure: Length of stenosis
timeFrame: at 6 months
measure: Length of stenosis
timeFrame: at 9 months
measure: Length of stenosis
timeFrame: at 12 months
measure: Estimated diameter of stenosis
timeFrame: at 1 month
measure: Estimated diameter of stenosis
timeFrame: at 3 months
measure: Estimated diameter of stenosis
timeFrame: at 6 months
measure: Estimated diameter of stenosis
timeFrame: at 9 months
measure: Estimated diameter of stenosis
timeFrame: at 12 months
measure: Endoluminal inflammation
timeFrame: at 1 month
measure: Endoluminal inflammation
timeFrame: at 3 months
measure: Endoluminal inflammation
timeFrame: at 6 months
measure: Endoluminal inflammation
timeFrame: at 9 months
measure: Endoluminal inflammation
timeFrame: at 12 months
measure: Number of dilation sessions
timeFrame: at 1 month
measure: Number of dilation sessions
timeFrame: at 3 months
measure: Number of dilation sessions
timeFrame: at 6 months
measure: Number of dilation sessions
timeFrame: at 9 months
measure: Number of dilation sessions
timeFrame: at 12 months
measure: Intervals between iterative dilations
timeFrame: at 1 month
measure: Intervals between iterative dilations
timeFrame: at 3 months
measure: Intervals between iterative dilations
timeFrame: at 6 months
measure: Intervals between iterative dilations
timeFrame: at 9 months
measure: Intervals between iterative dilations
timeFrame: at 12 months
measure: Digestive perforations
timeFrame: at 1 month
measure: Digestive perforations
timeFrame: at 3 months
measure: Digestive perforations
timeFrame: at 6 months
measure: Digestive perforations
timeFrame: at 9 months
measure: Digestive perforations
timeFrame: at 12 months
measure: Extent of pharyngeal stenosis
timeFrame: at 1 month
measure: Extent of pharyngeal stenosis
timeFrame: at 3 months
measure: Extent of pharyngeal stenosis
timeFrame: at 6 months
measure: Extent of pharyngeal stenosis
timeFrame: at 9 months
measure: Extent of pharyngeal stenosis
timeFrame: at 12 months
measure: Proportion of unanticipated adverse reactions
timeFrame: at day 0
measure: Proportion of unanticipated adverse reactions
timeFrame: at day 2
measure: Proportion of unanticipated adverse reactions
timeFrame: at day 5
measure: Proportion of unanticipated adverse reactions
timeFrame: at day 7
measure: Proportion of unanticipated adverse reactions
timeFrame: at one month
measure: Proportion of unanticipated adverse reactions
timeFrame: at 3 months
measure: Proportion of unanticipated adverse reactions
timeFrame: at 6 months
measure: Proportion of unanticipated adverse reactions
timeFrame: at 9 months
measure: Proportion of unanticipated adverse reactions
timeFrame: at 12 months
measure: Proportion of adverse reactions related to corticosteroid therapy
timeFrame: within 7 days
measure: C-Reactive Protein (CRP)
timeFrame: at day 0
measure: C-Reactive Protein (CRP)
timeFrame: at day 2
measure: C-Reactive Protein (CRP)
timeFrame: at day 5
measure: C-Reactive Protein (CRP)
timeFrame: at one month
measure: interleukin-1 (IL1)
timeFrame: at day 0
measure: interleukin-1 (IL1)
timeFrame: at day 2
measure: interleukin-1 (IL1)
timeFrame: at day 5
measure: interleukin-1 (IL1)
timeFrame: at one month
measure: interleukin-6 (IL-6)
timeFrame: at day 0
measure: interleukin-6 (IL-6)
timeFrame: at day 2
measure: interleukin-6 (IL-6)
timeFrame: at day 5
measure: interleukin-6 (IL-6)
timeFrame: at one month
measure: Tumour Necrosis Factor alpha (TNF alpha)
timeFrame: at day 0
measure: Tumour Necrosis Factor alpha (TNF alpha)
timeFrame: at day 2
measure: Tumour Necrosis Factor alpha (TNF alpha)
timeFrame: at day 5
measure: Tumour Necrosis Factor alpha (TNF alpha)
timeFrame: at one month
measure: Tissue Growth Factor Beta (TGF beta)
timeFrame: at day 0
measure: Tissue Growth Factor Beta (TGF beta)
timeFrame: at day 2
measure: Tissue Growth Factor Beta (TGF beta)
timeFrame: at day 5
measure: Tissue Growth Factor Beta (TGF beta)
timeFrame: at one month
measure: Galectin 3
timeFrame: at day 0
measure: Galectin 3
timeFrame: at day 2
measure: Galectin 3
timeFrame: at day 5
measure: Galectin 3
timeFrame: at one month
Other outcomes:
Locations:
Study officials:
References: