Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00518310
Status:
UNKNOWN
Last Update Posted:
2007-08-20
First Post:
2007-08-16
Brief Title:
Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis
Sponsor:
Thorax National Institute
Organization:
Thorax National Institute
Study Overview
Official Title:
Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis a Randomized Double-Blind Controlled Study
Status:
UNKNOWN
Status Verified Date:
2007-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Idiopathic pulmonary fibrosis IPF is a diffuse lung disease associated with the histological appearance of usual interstitial pneumonia UIP with an inexorably deteriorating clinical course Prognosis is poor reported median survival is less than 3 years The prevalence is estimated as being 3 to 10 per 100000 in different Western populations To date no pharmacological therapy has been proven to alter or reverse the pathogenic process of IPF Most treatments trials have been observational case series of small patient populations and very few have been randomized prospective and placebo-controlled
Two recent Cochrane reviews investigated the role of corticosteroids and other immunomodulatory agents and concluded that there is no evidence for their use in IPF Most current therapies are targeted to suppress the inflammatory component of the disease based on the theory that it would be chronic alveolar inflammation which leads to parenchymal remodeling and fibrosis Recently a hypothesis that has gained acceptance suggests that fibrosis may result directly from alveolar injury promoting an abnormal fibrogenic repair mediated by fibroblasts and myofibroblasts
One of the cytotoxic agents most widely used and better tolerated in the management of IPF is azathioprine Based upon limited data available and from a single small high quality randomized controlled trial RCT this drug appears to confer given in conjunction with prednisone a marginal long term survival advantage Since this combination therapy is associated serious adverse effect we planned to design a trial of low dose corticosteroid and azathioprine versus placebo in management of IPF evaluating progression-free survival
Our study hypothesis is Combined therapy with azathioprine and corticosteroids improves progression-free survival in patients with the diagnosis of IPF
Two recent Cochrane reviews investigated the role of corticosteroids and other immunomodulatory agents and concluded that there is no evidence for their use in IPF Most current therapies are targeted to suppress the inflammatory component of the disease based on the theory that it would be chronic alveolar inflammation which leads to parenchymal remodeling and fibrosis Recently a hypothesis that has gained acceptance suggests that fibrosis may result directly from alveolar injury promoting an abnormal fibrogenic repair mediated by fibroblasts and myofibroblasts
One of the cytotoxic agents most widely used and better tolerated in the management of IPF is azathioprine Based upon limited data available and from a single small high quality randomized controlled trial RCT this drug appears to confer given in conjunction with prednisone a marginal long term survival advantage Since this combination therapy is associated serious adverse effect we planned to design a trial of low dose corticosteroid and azathioprine versus placebo in management of IPF evaluating progression-free survival
Our study hypothesis is Combined therapy with azathioprine and corticosteroids improves progression-free survival in patients with the diagnosis of IPF
Detailed Description:
We will evaluate all adult patients consecutively referred from March 2005 to the Instituto Nacional del Tórax Thorax National Institute Santiago Chile for diagnostic evaluation of Pulmonary Fibrosis The routine evaluation will include when indicated the following steps
History
Age
Genre
Duration of symptoms before first consultation
Smoking status
Search for collagen vascular disease
Family history of pulmonary fibrosis
Occupational exposures
Drug ot toxic exposures
Physical examination search of crackles and finger clubbing
Laboratory data
Complete blood bell count
BUN
Creatinine
Liver enzymes
Antinuclear antigens
Erythrocyte sedimentation rate
Rheumatoid factor
HIV
Antineutrophil cytoplasmic antibody in appropiate clinical setting
Antiglomerular basement antibody in appropiate clinical setting
Modified Medical Research Council Dyspnea Scale MMRC 10
Chronic Respiratory Questionnaire CRQ 11
Pulmonary function tests
Spirometry
Plethismographic lung volumes
DLco
Composite physiologic index 12
Exercise testing
Six-Minute Walk Test 6MWT
Resting and 6 minute SpO2
Presence or absence of desaturation to 88 or lower at the end of the six minute walk 13
Walked distance
Pre and post modified Borg dyspnea scores
Timed walk test 14
Arterial blood gas analysis in rest and exercise calculating the difference between alveolar and arterial oxygen tension PA-aO2 at rest and after exercise
Radiologic studies
Chest radiography
HRCT
Definite or probable idiopathic pulmonary fibrosis 15
Definitive criteria presence of lung volume reduction reticular abnormalities traction bronchiectasis or both with a basal and peripheral predominance the presence of honeycombing with a basal and peripheral predominance and the absence of atypical features of usual interstitial pneumonia - micronodules peribronchovascular nodules consolidation isolated nonhoneycombing cysts ground-glass attenuation or if present less extensive than the reticular opacity and mediastinal adenopathies or if present too limited to be visible on a chest radiography
Probable criteria presence of a bilateral predominantly basal and subpleural reticular pattern with subpleural cysts honeycombing traction bronchiectasis or both in the absence of atypical features of UIP
Scoring of the extent of lung fibrosis 16
Bronchoscopy
Bronchoalveolar lavage cellular analysis and CD4CD8 ratio
Transbronchial biopsy
Surgical lung biopsy
Number
SiteSide
Type of surgery open vs thoracoscopic
Histologic features 3
Those patients with IPF diagnosed on the basis of clinical and radiographic criteria alone according to the ATSERS consensus committee 3 andor with a biopsy proven histological pattern of UIP will be selected to the randomization process after they have signed the written informed consent
History
Age
Genre
Duration of symptoms before first consultation
Smoking status
Search for collagen vascular disease
Family history of pulmonary fibrosis
Occupational exposures
Drug ot toxic exposures
Physical examination search of crackles and finger clubbing
Laboratory data
Complete blood bell count
BUN
Creatinine
Liver enzymes
Antinuclear antigens
Erythrocyte sedimentation rate
Rheumatoid factor
HIV
Antineutrophil cytoplasmic antibody in appropiate clinical setting
Antiglomerular basement antibody in appropiate clinical setting
Modified Medical Research Council Dyspnea Scale MMRC 10
Chronic Respiratory Questionnaire CRQ 11
Pulmonary function tests
Spirometry
Plethismographic lung volumes
DLco
Composite physiologic index 12
Exercise testing
Six-Minute Walk Test 6MWT
Resting and 6 minute SpO2
Presence or absence of desaturation to 88 or lower at the end of the six minute walk 13
Walked distance
Pre and post modified Borg dyspnea scores
Timed walk test 14
Arterial blood gas analysis in rest and exercise calculating the difference between alveolar and arterial oxygen tension PA-aO2 at rest and after exercise
Radiologic studies
Chest radiography
HRCT
Definite or probable idiopathic pulmonary fibrosis 15
Definitive criteria presence of lung volume reduction reticular abnormalities traction bronchiectasis or both with a basal and peripheral predominance the presence of honeycombing with a basal and peripheral predominance and the absence of atypical features of usual interstitial pneumonia - micronodules peribronchovascular nodules consolidation isolated nonhoneycombing cysts ground-glass attenuation or if present less extensive than the reticular opacity and mediastinal adenopathies or if present too limited to be visible on a chest radiography
Probable criteria presence of a bilateral predominantly basal and subpleural reticular pattern with subpleural cysts honeycombing traction bronchiectasis or both in the absence of atypical features of UIP
Scoring of the extent of lung fibrosis 16
Bronchoscopy
Bronchoalveolar lavage cellular analysis and CD4CD8 ratio
Transbronchial biopsy
Surgical lung biopsy
Number
SiteSide
Type of surgery open vs thoracoscopic
Histologic features 3
Those patients with IPF diagnosed on the basis of clinical and radiographic criteria alone according to the ATSERS consensus committee 3 andor with a biopsy proven histological pattern of UIP will be selected to the randomization process after they have signed the written informed consent
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None