Esophageal Replacement With a Decellularized Human Esophagus Graft (ESOGRAFT)

Remplacement de l'œsophage Par Une Greffe d'œsophage Humain décellularisé

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Stenosis
• Intervention / Treatment: Other: Replacement of the esophagus with a decellularized human esophagus graft

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Phone Number: +33 +33142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Pierre Cattan, MD PhD; Phone Number: +33 +33142499116; Email: pierre.cattan@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Esophagus replacement

Other: Replacement 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity/mortality	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	At 3 months after surgery
Nutritional autonomy	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	At 12 months after esophageal replacement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the procedure	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.	At 12 months after esophageal replacement
Presence of complete re-epithelialization, and integration into the native esophagus	Assessed by endoscopy	At 3 months after surgery
Presence of complete re-epithelialization, and integration into the native esophagus	Assessed by CT scan with gel ingestion and intravenous contrast injection	At 12 months after surgery
Normal bolus transit	Assessed by barium deglutition	At 6 months after surgery
Normal bolus transit	Assessed by barium deglutition	At 12 months after surgery
Esophageal manometry		At 12 months after surgery
Percentage of procedures interrupted for logistical reasons	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	Up to 14 months
Overall survival and Safety of procedure	Patient survival at 12 months regardless of cause of death	At 12 months after surgery
Impact of procedure on quality of life	EORTC QLQ-OG25 module Score varying between 25 and 100, the higher the score the more severe the symptoms	At 6 months after surgery
Impact of procedure on quality of life	EORTC QLQ-OG25 module Score varying between 25 and 100, the higher the score the more severe the symptoms	At 12 months after surgery
Impact of procedure on quality of life	SF12V2 modules It is a 12 items score varying from to 0 to 100. The higher the score, the better the quality of life	At 6 months after surgery
Impact of procedure on quality of life	SF12V2 modules It is a 12 items score varying from to 0 to 100. The higher the score, the better the quality of life	At 12 months after surgery
Estimating the cost of the procedure for one patient	-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.	At 12 months
Estimating the cost of the procedure for target population	-Simulation using trial data of costs for all patients with esophageal transplant indication	At 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Tissue engineering; Esophageal stent; Esophageal stenosis; Esophageal replacement; Caustic injury; Anastomotic stenosis
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Constriction, Pathologic; Esophageal Stenosis
• Other Study ID Numbers: APHP220793

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