Montelukast in Bronchiolitis Obliterans Syndrome

Study Overview
=================
Brief Summary
-----------------
Chronic rejection (or Bronchiolitis Obliterans syndrome-BOS) is a major cause of mortality and morbidity after lung transplantation. Because montelukast has been shown to be of some efficacy in a similar disease (Obliterative Bronchiolitis after bone marrow transplantation), the investigators would like to test if montelukast can indeed slow down the progression of chronic rejection after lung transplantation.

Detailed Description
-----------------
Prospective, interventional, randomized, double-blind, placebo-controlled trial. Clinical setting (tertiary University Hospital). Investigator-driven, no pharmaceutical sponsor. Lung transplant recipients. Add-on of study-drug (placebo or montelukast) to 'standard of care' 1:1 inclusion ratio (placebo:montelukast). Randomisation at diagnosis of chronic rejection after informed consent.

Official Title
-----------------
A Randomized, Double Blind, Placebo Controlled Trial With Montelukast to Treat Bronchiolitis Obliterans Syndrome After Lung Transplantation

Conditions
-----------------
Bronchiolitis Obliterans, Lung Transplantation, Graft Rejection

Intervention / Treatment
-----------------
* Drug: Montelukast


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of fBOS Signed informed consent Age at least 18 years old at moment of transplantation Able to take oral medication Exclusion Criteria: Retransplantation Previous organ transplantation Multi organ transplantation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: montelukast sodium<br>Daily treatment with 10 mg montelukast after diagnosis of fibroproliferative BOS (fBOS) which is the low neutrophilic phenotype within BOS | Drug: Montelukast<br>* After diagnosis of fBOS every day an oral capsule with 10 mg montelukast of placebo<br>* Other names: Montelukast TEVA;|
| Placebo Comparator: placebo<br>Lactose monohydricum Ph.Eur. | Drug: Montelukast<br>* After diagnosis of fBOS every day an oral capsule with 10 mg montelukast of placebo<br>* Other names: Montelukast TEVA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival/retransplantation rate after diagnosis of BOS |  | 1 year after diagnosis | 
| survival/retransplantation rate at 2 years after diagnosis |  | 2 years after diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Obstructive and restrictive pulmonary function evolution |  | during 1 and 2 years of treatment | 
| Bronchoalveolar lavage fluid (BAL) | BAL will be used to assess cellularity, protein and mRNA concentration and microbiology | during 1 and 2 years of treatment | 
| peripheral blood | peripheral blood will be used to assess C-reactive protein, protein and mRNA concentration and fibrocytes content | during 1 and 2 years of treatment | 
| Cytomegalovirus (CMV) and non-CMV infection rates |  | during 1 and 2 years of follow up | 
| Acute rejection and lymphocytic bronchiolitis rates |  | after 1 and 2 years of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
montelukast, cysteinyl leukotriene, lung transplantation, bronchiolitis obliterans syndrome