Esophageal Stenosis
Conditions
Keywords
Tissue engineering, Esophageal replacement, Esophageal stenosis, Caustic injury, Radiotherapy, Anastomotic stenosis, Esophageal stent
Brief summary
The aim of the study is to analyze over a 12 month-period, the safety and the efficacy of a circumferentiel oesophageal replacement of the esophagus by a decelularized human esophagus, in 24 patient with a short esophageal stenosis refractory to endoscopic dilatations.
Interventions
OTHERReplacement of the esophagus with a decellularized human esophagus graft
The Decellularized Human Esophagus (DHE) will be surgically implanted under general anesthesia via right or left thoracotomy or cervicotomy, depending on the location of the stenosis, to replace the esophageal defect created by resection of the stenosis. An omentoplasty is performed laparoscopically beforehand to provide secondary coverage of the graft area. A temporary esophageal stent is placed endoscopically to cover the DHE and the two anastomoses for a period of 3 months, to prevent the development of an anastomotic fistula and stenosis of the graft area.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Open-label, non-comparative, phase I/II, single-arm, multicenter trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18 to 65 * Caustic, traumatic, anastomotic, post-operative, radiation-induced or post-endoscopic (mucosal resection, submucosal dissection) benign esophageal stricture refractory to endoscopic dilatation. * For women: effective contraception for the entire duration of the study (from signature of consent to end of follow-up) * Affiliated or beneficiary of a social security scheme. * Free written consent signed by the participant and the investigator.
Exclusion criteria
* Weight loss \> 10% of body weight over last 3 months * Stenosis \> 5 cm in length * Multiple strictures * Esophageal mouth stenosis * Anterior surgery close to the operative zone * Complete anterior omentectomy * Tumour stenosis or progressive tumour pathology * Non-stabilized psychiatric disorders * Participation in another interventional study * Pregnant or breast-feeding women * Women of childbearing age without effective contraceptive measures: All women of childbearing age must have a negative pregnancy test prior to treatment and must agree to maintain highly effective contraception using contraceptive measures from the date of consent until 12 months due to the risks associated with anesthesia during endoscopy * Uncontrolled sepsis * Related to the transplant procedure * ASA score ≥ 3, * Severe respiratory insufficiency (FEV1 \< 1 L), * Decompensated hepatic cirrhosis or presence of esophageal varices, * Chronic renal insufficiency (creatinine \> 1.25 N), * Myocardial infarction less than 6 months old or progressive heart disease, * WHO general condition \> 2, * Weight loss \>20% not recovered after renutrition. * Contraindication to general anaesthesia, analgesics and antibiotics. * Conditions requiring long-term immunosuppressive or corticosteroid treatment. * Patients under curatorship or guardianship
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morbidity/mortality | At 3 months after surgery | Safety criterion : morbidity/mortality defined by : Refractory stenosis, leaking, sepsis, stent migration, death, complete rupture of anastomoses, uncontrolled mediastinal sepsis requiring removal of the substitute and/or esophagectomy, delamination of the tissue graft, tracheobronchial wound intra-operatively or oesotracheal fistula postoperatively, upper digestive obstruction after stent removal preventing any attempt to dilate the graft zone, or upper digestive obstruction after stent removal preventing any attempt to dilate the graft zone |
| Nutritional autonomy | At 12 months after esophageal replacement | Efficacy criterion: nutritional autonomy at 12 months after esophageal replacement defined as stable weight with exclusive oral nutrition and without esophageal stenting for at least 3 months, and without persistent symptomatic scar stenosis after 5 endoscopic dilatation sessions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normal bolus transit | At 6 months after surgery | Assessed by barium deglutition |
| Esophageal manometry | At 12 months after surgery | — |
| Percentage of procedures interrupted for logistical reasons | Up to 14 months | Logistical reasons are defined as : * An incident during transport from the Human Tissue Bank to the operating room, resulting in the loss of the graft * Accidental rupture of graft packaging, with risk of loss of sterility * An incident occurring during the graft thawing procedure |
| Safety of the procedure | At 12 months after esophageal replacement | The morbidity and mortality of the procedure will be defined by the occurrence of a complication such as leakage, sepsis, recurrent paralysis, esophageal stricture refractory to dilatation, anastomotic fistula, sepsis, esophageal perforation, cardio-respiratory complication (pneumopathy, pleural effusion, pulmonary embolism, AC/FA, infarction), death, tissue graft disintegration, postoperative tracheobronchial wound or oesotracheal fistula, or upper digestive obstruction after stent removal preventing any attempt to dilate the graft zone), for 12 months from the date of surgery. |
| Impact of procedure on quality of life | At 6 months after surgery | EORTC QLQ-OG25 module Score varying between 25 and 100, the higher the score the more severe the symptoms |
| Estimating the cost of the procedure for one patient | At 12 months | -Direct medical costs of the procedure: constitution (tissue engineering), storage and transport of the esophageal stent, hospital stay for graft surgery, emergency room visits, scheduled or unscheduled re-hospitalizations, follow-up in hospital consultations, scheduled or unscheduled outpatient physician visits, outpatient biological procedures, outpatient medical imaging, drug prescriptions, transport and coordination time by the expert team. |
| Estimating the cost of the procedure for target population | At 12 months | -Simulation using trial data of costs for all patients with esophageal transplant indication |
| Overall survival and Safety of procedure | At 12 months after surgery | Patient survival at 12 months regardless of cause of death |
| Presence of complete re-epithelialization, and integration into the native esophagus | At 3 months after surgery | Assessed by endoscopy |
Contacts
Primary ContactPierre Cattan, MD PhD
Backup ContactJérôme Lambert, MD PhD
Outcome results
None listed