Early Detection and Management of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation
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|ClinicalTrials.gov Identifier: NCT03072849|
Recruitment Status : Recruiting
First Posted : March 7, 2017
Last Update Posted : March 7, 2017
|Condition or disease||Intervention/treatment|
|Bronchiolitis Obliterans Syndrome||Procedure: Pulmonary function testing Drug: FAM Therapy|
Bronchiolitis obliterans syndrome (BOS) is an inflammatory condition of the lungs that leads to obstructive physiology, irreversible fibrosis of terminal bronchioles, and obliteration of the small airways. In both children and adults, the prevalence of BOS is approximately 6% in those with chronic graft-vs-host disease (cGVHD), although this may be a gross underestimation given current diagnostic guidelines. Once diagnosed, the prognosis is extremely unfavorable. BOS carries a mortality rate of approximately 40-60%, with a five year survival rate of 13%.
Early on, BOS is symptomatically silent. Once symptoms are present, there is a high likelihood of irreversible disease regardless of the combination of immune suppression used. Given these circumstances, early diagnosis is of utmost importance, and can be characterized by an isolated and subclinical decline in lung function. Recent studies have suggested that early decline in lung function on pulmonary function testing (PFT) may be representative of developing BOS.
Due to the lack of consistent screening and diagnostic criteria, many patients with evolving BOS elude a timely diagnosis, thereby jeopardizing their chance of survival. In response, several experts have recommended frequent PFT screening and a modified, less stringent set of diagnostic criteria with the goal of establishing earlier diagnosis and timely intervention.
Traditionally, treatment of BOS has included aggressive immunosuppression, leaving patients at risk for life-threatening invasive infections, multi-system co-morbidities, and the threat of lung transplantation. Recent studies have demonstrated that early management with agents such as inhaled corticosteroids (ICS), macrolides, and leukotriene receptor antagonists (LTRA) can lead to improvements in both lung function and clinical symptoms.
This study aims to evaluate the utility of frequent and routine pulmonary surveillance in pediatric patients who have undergone allogenic HSCT. Our prospective study design provides a novel framework for the implementation of standardized lung function screening every three months in the first two years following HSCT. With this, we hypothesize that standardized PFT screening will improve diagnostic sensitivity and allow for earlier intervention in patients with evolving airway obstruction and BO.
This study also aims to evaluate the efficacy of inhaled fluticasone, azithromycin, and montelukast (FAM therapy) in the management of early airflow obstruction in pediatric patients following allogenic HSCT. Early airflow obstruction is defined by pulmonary function testing (FEV1 decline of ≥10% predicted with a FVC <0.8). With this, we hypothesize that FAM therapy will attenuate the progression of airflow obstruction and improve lung function in those with irreversible airflow obstruction at one and two years when compared to historical controls.
|Study Type :||Observational|
|Estimated Enrollment :||40 participants|
|Official Title:||Early Detection and Management of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||April 2017|
|Estimated Study Completion Date :||April 2019|
Stem Cell Transplant Recipients
Pediatric patients ages 6-18 years who have received allogenic hematopoietic stem cell transplant for any reason.
Procedure: Pulmonary function testing
Each enrolled patient will receive pulmonary function testing every three months. Pulmonary function testing includes spirometry, plethysmography, and diffusion capacity measurements.
Other Names:Drug: FAM Therapy
All patients who have evidence of early airflow obstruction on pulmonary function testing will be started on FAM therapy. Early airflow obstruction is defined by a FEV1 decline of ≥10% predicted in addition to a FVC <0.8.
- Lung function [ Time Frame: 2 years ]Change in lung function at 12 and 24 months post-HSCT
- Survival [ Time Frame: 2-4 years ]Overall survival at 2 years post-HSCT
- Risk factor assessment [ Time Frame: 2 years ]To identify risk factors for the development of BOS
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03072849
|Contact: Jennifer Schneiderman, MD, MSemail@example.com|
|Contact: Matthew F Abts, MDfirstname.lastname@example.org|
|United States, Illinois|
|Ann & Robert H Lurie Children's Hospital of Chicago||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Jennifer Schneiderman, MD, MS 312-227-4000 email@example.com|
|Contact: Joseph Laskowski (312)227-4000 firstname.lastname@example.org|