Biodegradable Stents in the Management of Stenoses of the Large Airways

Study Overview
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Brief Summary
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The objective of this project is to determine whether biodegradable polydioxanone stents are efficient in the treatment of adult patients with tracheobronchial stenoses.

Detailed Description
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Background: The ideal airway stent has yet to be developed. Biodegradable (BD) stents are made of knitted polymer fibers that degrade when placed in the body; extraction of the device is, therefore, unnecessary. Several in vitro and in vivo studies of tracheal BD stents composed of various materials have been conducted. Polydioxanone is a biodegradable polymer in the polyester family, which has attracted a lot of interest due to its exquisite biocompatibility and is currently available on the market in the form of absorbable suture material. It is degraded by hydrolysis (of its ester bonds), which is accelerated under low potential of Hydrogen (pH) conditions, into harmless degradation products. Polydioxanone tracheal stents appear to be well tolerated by the tracheal mucosa, retain their mechanical strength for as long as 6 weeks, and, in animal models, completely degrade after approximately 15 weeks. They have been successfully used in humans as mechanical support for tracheal transplants, during treatment of obstructive airway complications after lung transplantation, and in children with airway stenosis. Hypotheses: Biodegradable stents can be used in adult patients as a temporary mechanical support of narrowed airways, they allow healing of the airways or secure the airways until another (anticancer, anti-inflammatory) therapy manages the cause of the narrowing. Biodegradable stents are expected to have advantages over classical stents, namely good biocompatibility, fair adaptation to the anatomy of the airways, they do not limit the transportation of secretions substantially. Objectives: The primary objective of this study is to show that BD stents can be safely used and are effective in the treatment of adult patients with tracheal narrowings. The secondary objectives are: to observe and analyze mucosa - BD stent interaction, to assess degradation of stents and its consequences. Design: Prospective interventional study conducted in three hospitals in the Czech Republic. Methods: The investigators intend to enroll adult participants suffering from significant large airway stenoses in which the stenting is generally considered to be effective. Every participant is reviewed by at least two interventional pulmonologists and a thoracic surgeon to determine the best therapeutic option. Bronchoscopy and computed tomography of the trachea is considered essential to confirm the diagnoses. All participants sign an informed consent form prior to undergoing the procedure. During the stent implantation, the trachea is intubated with a rigid bronchoscope, participants are placed under total intravenous anesthesia and jet ventilation. The investigators intend to use self-expandable, biodegradable, polydioxanone tracheal stents, the SX-ELLA Stent DV Tracheal (DV Stent), manufactured by ELLA-CS, s.r.o., Hradec Kralove, Czech Republic. Stent is standardly equipped with radiopaque markers at distal and proximal end. It is delivered in sterile packed, separately from original delivery system into which the stent immediately before implantation is placed. As mentioned, stent is made of synthetic polymer - braided polydioxanone fiber widely used for absorbable surgical suture. The suture has successfully been used in the surgery, orthopedics and dental surgery for more than 25 years. It is known that the material is subjected to the bulk hydrolytic degradation in the body. No toxic substances arise within the degradation process. The ultimate degradation substance is 2-hydroxyacetic acid that is finally metabolized to water and carbon dioxide. The data about local reaction produced by polydioxanone implants, incl. buried sutures are contradictory. Majority of them report very low tissue reaction. The first bronchoscopy follow up is carried out during the first post-implantation week, additional follow-ups (including clinical evaluation, bronchoscopy, basic spirometry, and chest X-ray if needed) are performed on a monthly or as-needed basis. If the restenosis threatens, the participant can be given another polydioxanone stent, as well as, he or she can be treated using mechanical removal of obstacles, balloon dilation, laser therapy and electrocautery. Results are analyzed continuously, final evaluation is intended to be performed after reaching a sufficient number of participants. This includes statistical analysis of overall results in participants after complete stent degradation, assessment of major clinical signs and functional parameters, and especially, evaluations of endoscopic findings.

Official Title
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Biodegradable Stents in the Management of Stenoses of the Large Airways

Conditions
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Tracheal Stenosis

Intervention / Treatment
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* Device: SX-ELLA Stent DV Tracheal (DV Stent)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: significant large airway stenoses benign tracheobronchial stenosis of any origin in participants who can not go for surgery, or who refuse surgical treatment benign tracheobronchial stenoses of any origin when the surgery is planed after some delay, benign tracheobronchial stenoses when the effect of anti- inflammatory or anti-infective treatment is expected malignant tracheobronchial stenoses due to extrinsic compression when exhausted curative modalities malignant stenoses from extrinsic compression in participants undergoing the actinotherapy or receiving systemic anticancer therapy Exclusion Criteria: stenoses of any origin which can be treated primarily surgically stenoses caused by intraluminal growth of tumor, tracheoesophageal or bronchoesophageal fistulas pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: biodegradable stent<br>endoscopic implantation of biodegradable airway stent, the SX-ELLA Stent DV Tracheal (DV Stent) | Device: SX-ELLA Stent DV Tracheal (DV Stent)<br>* The trachea is intubated with a rigid bronchoscope while participants are placed under total intravenous anesthesia and jet ventilation. The delivery apparatus containing the stent is introduced through a rigid tube to the desired depth under visual control. Then the stent is deployed and its position is determined and, if necessary, stent is repositioned using rigid forceps. In-stent balloon dilation is carried out. If needed, thoracic surgeon can secure the stent in place via external (percutaneous) fixation: one suture is passed through the stent, the tracheal wall, soft tissues, and skin; the suture is then knotted on the skin of the neck. The suture is removed two to three weeks after implantation.<br>* Other names: DV Stent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| airway patency during the presence of the stent in the airways | Scheduled bronchoscopies, trachea is, for the purposes of the study, classified according to Freitag's recommended adapted classification system (Freitag L. et al. A proposed classification system of central airway stenosis, Eur Respir J 2007; 30:7-12). | residence time of the stent in the airways, i.e. as long as no stent material is found, up to 180 days after implantation, since then the stent is not considered to provide any mechanical support | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of complications: infection, bleeding, migration, obstructive granulation tissue formation, sudden restenosis (of any origin, unexpected in relation to the degree of the stent degradation) |  | residence time of the stent in the airways (i.e. as long as no stent material is found, up to 180 days after implantation, since then the stent is not considered to provide any mechanical support) and 6 months thereafter | 
| evaluation of forced expiratory volume in 1 second (FEV1) | FEV1 (in liters and % predicted values) measurements within follow-ups. | residence time of the stent in the airways (i.e. as long as no stent material is found, up to 180 days after implantation, since then the stent is not considered to provide any mechanical support) and 6 months thereafter | 
| evaluation of forced vital capacity (FVC) | FVC (in liters and % predicted values) measurements within follow-ups. | residence time of the stent in the airways (i.e. as long as no stent material is found, up to 180 days after implantation, since then the stent is not considered to provide any mechanical support) and 6 months thereafter | 
| airway patency after complete degradation of the stent or loss of majority support functions | Scheduled bronchoscopies, trachea is, for the purposes of the study, classified according to Freitag's recommended adapted classification system (Freitag L. et al. A proposed classification system of central airway stenosis, Eur Respir J 2007; 30:7-12). | six months, beginning after identifying the complete degradation of the stent or 180 days after implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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absorbable implants, stents, bronchoscopy, polydioxanone