Clinical trial NCT04330846: Prospective Multicenter Randomized Comparative Study of the Treatment of de Novo Stenosis in Chron's Disease.
Official title: Prospective Multicenter Randomized Comparative Study of the Treatment of de Novo Stenosis in Crohn's Disease. Endoscopic Treatment (Self-expanding Metal Prosthesis/Ballon Dilation) vc Surgical Resection (ENDOCIR STUDY)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Crohn Disease
Keywords: crohn
Lead sponsor: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective multicenter randomized comparative study of the treatment of de novo stenosis due to CD, comparing endoscopic treatment (stent or EBD) vs. surgical resection (SR).

The type of endoscopic treatment will be initially with EBD and if a failure treatment occurred then a SEMS will be placed.
Primary purpose: DIAGNOSTIC

Brief summary: Stenosis is one of the most frequent complications in patients with Crohn's disease (CD), causing greater morbidity and increasing the probability of repeated surgery and short bowel syndrome (1-3). Endoscopic balloon dilation (EBD) is clearly the treatment of choice for short stenoses located at the anastomosis of previous surgeries (4-6). However, there is no scientific evidence for determining the most appropriate treatment for de novo stenosis less than 10 cm in length (surgical versus endoscopic treatment), both in terms of efficacy and complications. Neither has it been established which of these two approaches has a greater impact on the quality of life of patients and on costs.

Detailed description: In many cases, a surgical approach allows for the removal of the entire inflamed intestine. However, the percentage of post-surgical recurrence per year after surgery is 80-85% (7), decreasing to 40% in patients who begin preventive immunosuppressive treatment in the immediate post-surgery period (8). This means that more than 40% of patients will require combined immunosuppression to keep CD under control one year after surgery. Endoscopic treatment does not remove the affected intestine. However, it has a long-term therapeutic efficacy of 50-60% with a very low percentage of complications (4-6%).

A large number of studies have shown that patients' quality of life improves when CD is properly controlled, either through medical or surgical treatment (9). However, there are no studies evaluating the quality of life of patients after endoscopic treatment.

Neither are there comparative studies of the costs of the two procedures. However, a recent study comparing the cost of 38 endoscopic procedures with their surgical equivalent suggested that, in most cases, the cost of endoscopic treatment is four times lower (10).

The European Crohn's and Colitis Organization (ECCO) guidelines on the management of de novo stenosis in patients with CD recommend surgery as the first option, based on expert opinion (Level of Evidence 4), although there are no studies comparing the two treatment modalities (11,12).

A Spanish multicenter study coordinated by researchers involved in the present project (Andujar X, et al)(13), which included the largest published series of endoscopic treatment with dilation in patients with CD to date, shows that therapeutic success with EBD in de novo stenoses is achieved in a large percentage of cases, with results similar to those obtained in post-surgical stenoses (73% vs 84%).

In addition, CD stenoses can be treated effectively with self-expanding metal stents (SEMS), and it has been suggested that these may be particularly indicated in patients who are refractory to balloon dilation, including both de novo and anastomotic stenosis patients (14-17). Therefore, in order to compare the efficacy of these two endoscopic treatments, the PROTDILAT study (IP: C Loras. Project FIS nº Pl13/01226 and Clinical Trials. Gov nº NCT02395354) was designed, and is currently in the final manuscript writing phase (100 patients included). The final results (Andújar X, UEGW 2019)(18) confirm that both procedures are effective and safe in the treatment of both post-surgical and de novo stenosis, while showing the therapeutic superiority of EBD over SEMS when the results are evaluated globally (80.5 vs 51.3 %; primary end point). However, this difference is not observed in the subanalysis of patients with stenosis ≥4 cm (LBD: 66.7% vs PMA: 63.6%) but with a significantly lower cost in EDB treatment (EDB 1,212.41 euros vs PMA 3,615.07 euros). Therefore, SEMS may have a role to play in longer stenosis in which EBD has proven to be less efficacious.

This work has been conceived as an exploratory proof of concept study, given that there are currently no studies comparing surgical and endoscopic approaches and it is therefore difficult to calculate the adequate sample size.

Eligibility criteria: Inclusion Criteria:

* 18-80 years of age.
* Crohn's disease with predominantly de novo fibrotic stenosis\* confirmed by endoscopic and radiological tests, accessible by endoscopy (colonoscopy).
* Patients with known stenosis previously treated with stenting and/or dilation performed over one year before the date of inclusion.
* Symptomatology of intestinal occlusion-subocclusion.
* Refractoriness to conventional medical treatment (non-response to the usual accelerated step-up therapeutic approach).
* Stenosis length \< 10 cm.
* Maximum of 2 stenoses.
* Informed consent from patient.

Exclusion Criteria:

* No informed consent from the patient.
* Complicated stenosis with abscess, fistula or significant activity associated with CD not limited to the area of the stenosis.
* Patients with known stenosis previously treated with stenting and/or dilation performed \< 1 year before the date of inclusion.
* Pregnancy or lactation.
* Any clinical situation that prevents the performance of endoscopy or surgery.
* Stenosis not accessible by endoscopy.
* Asymptomatic patient.
* Stenosis length ≥ 10 cm.
* Presents with \> 2 stenoses.
* Severe coagulation disorders (platelets \< 70000; INR \> 1.8).

Primary outcomes:
measure: Quality of life of patients
timeFrame: One year of follow-up
Secondary outcomes:
measure: Percentage of patients with clinical recurrence
timeFrame: One year of follow-up
measure: Percentage of complications
timeFrame: One year of follow-up
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Manresa
country: Spain
facility: Althaia, xarxa assistencial universitaria de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Consorci Corporació Sanitària Parc Taulí
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Moisès Broggi
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Cáceres
country: Spain
facility: Hospital Universitario de Cáceres
city: Girona
country: Spain
facility: Clínica Girona
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Inca
country: Spain
facility: Hospital de Inca
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Terrassa
country: Spain
facility: Hospital de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari La Fe
Study officials:
affiliation: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
name: Carme Loras
role: PRINCIPAL_INVESTIGATOR
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