Idiopathic Pulmonary FibrosisNCT00518310
Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis
A study testing AZAPRED in people with Idiopathic Pulmonary Fibrosis, run by Thorax National Institute at 1 site in Chile.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 79 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- AZAPRED
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChile
- Study dates
- May 2005to Dec 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 45 and 79 years of age.
- Clinical symptoms of IPF for at least 3 months.
- Forced vital capacity (FVC) between 50 to 90% of the predicted value.
- DLco at least 35% of the predicted value.
- PaO2 > 55 mm Hg while breathing ambient air at rest.
- High-resolution computed tomography (HRCT) showing definite or probable criteria of IPF.
Who cannot join
- Clinically significant exposure to known fibrogenic agents (birds, molds, hot tubes, asbestos, radiation and drugs known to cause pulmonary fibrosis (amiodarone, nitrofurantoin, bleomicin,etc)).
- History of neurofibromatosis, Hermansky-Pudlak syndrome, metabolic storage disorders, etc.
- History of fever, weight loss, myalgias, arthralgias, skin rash, arthritis.
- Active infection within one week before enrollment.
- Alternative cause of interstitial lung disease.
- Ratio of the forced expiratory volume in one second (VEF1) to FVC of less than 0.6 after the use of a bronchodilator.
Show all 22Show fewer
- Residual volume more than 120% of the predicted value (when available).
- More than 20% of lymphocytes or eosinophils in bronchoalveolar lavage (BAL) (when available).
- Granulomas, infection or malignancy in the transbronchial or surgical biopsy (when available).
- Previous therapy with azathioprine, prednisolone (>0.5 mg/kg/day or more for at least 3 months), cyclophosphamide or novel biotech drugs.
- Unstable cardiovascular or neurologic disease.
- Uncontrolled diabetes.
- Pregnancy.
- Lactation.
- Likelihood of death, as predicted by the investigator, within the next year.
- White cell blood count < 4000/mm3.
- Platelet count < 100000/mm3.
- Hematocrit < 30% or > 59%.
- Liver enzymes more than 3 times the upper limit of the normal range.
- Creatinine level > 1.5 mg/dL.
- Albumin level < 3 g/dL.
- Refusal to sign informed consent by patient or guardian.
Trial locations and contacts
1 site in 1 country.
Alvaro Undurraga, MD contact
Chile1 site, 1 recruiting
- Recruiting
Instituto Nacional del Tórax
Santiago, RM
Jeannie Hinrichsen, RN, jhinrichsen@torax.cl
Carmen L Naranjo, cnaranjo@torax.cl
About this study
Official title: Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis: a Randomized, Double-Blind, Controlled Study
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 100.000 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.
Read more
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.
Read the 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 (P(A-a)O2) 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 CD4/CD8 ratio.
- Transbronchial biopsy.
- Surgical lung biopsy:
- Number
- Site/Side
- 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 ATS/ERS consensus committee (3), and/or with a biopsy proven histological pattern of UIP, will be selected to the randomization process, after they have signed the written informed consent.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- Placebo, AZAPRED
- Keywords
- Interstitial lung disease, Idiopathic pulmonary fibrosis, Usual interstitial pneumonia, Cryptogenic fibrosing alveolitis, Therapy, Azathioprine, Steroids, Glucocorticoids, Corticosteroids, Prednisone
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
AZAPREDDrug
The initial dose of prednisone will be 0.5 mg/kg/day for 4 weeks, then 0.25 mg/kg/day for 8 weeks. The dose will continue to decrease at a rate of 5 to 10 mg per week, to a dose of 0.25 or 0.125 mg/kg/day. Azathioprine will be given at a dose of 2-3 mg/kg/day (max 100 mg).
| Study group | Role | What they receive |
|---|---|---|
| 0 | Placebo comparator | Placebo Receives: Drug: Placebo |
| 1 | Active comparator | Azathiprine Prednisone Receives: Drug: AZAPRED |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival, defined as free of death or a decrease from baseline in the FVC of at least 10%.
Measured: 2 years
Secondary outcomes (12)
Number of Acute Exacerbations of IPF.
Measured: 2 years
Health Related Quality of life, measured with the Chronic Questionnaire (CRQ).
Measured: 2 years
PO2 at rest and at exercise from baseline.
Measured: 2 years
P(A-a)O2 at rest and at exercise from baseline.
Measured: 2 years
Predicted FEV1 from baseline.
Measured: 2 years
Forced expiratory volume in one second (FEV1) to FVC from baseline.
Measured: 2 years
Plethysmographic lung volumes from baseline.
Measured: 2 years
Diffusion capacity for carbon monoxide (DLco) from baseline.
Measured: 2 years
Six-Minute Walk test, from baseline: resting and 6 minute SpO2, presence or absence of desaturation to 88% or lower at the end of the six minute walk, walked distance d. Pre and post modified Borg dyspnea scores
Measured: 2 years
Scoring of extent of lung fibrosis on HRCT, according to two independent chest radiologists, form baseline.
Measured: 2 years
Number and severity of adverse effects.
Measured: 2 years
Number of protocol drop outs.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2007 (estimated)
- Study startMay 2005
- Study completionDec 2008 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thorax National Institute
- Sponsor type
- Other government
- Collaborators
- Sociedad Chilena de Enfermedades Respiratorias, Servicio de Salud Metropolitano Oriente, Ministerio de Salud de Chile
- Investigators
- Florenzano Matías, MD, Principal investigator, Clínica Las Condes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00518310
- Sponsor's protocol ID
- 10351
- Status last verified
- Aug 2007
- First submitted
- 16 Aug 2007
- Last updated
- 20 Aug 2007
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis: a Randomized, Double-Blind, Controlled Study
- ClinicalTrials.gov ID
- NCT00518310
- Acronym / sponsor ID
- 10351
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Interstitial lung disease, Idiopathic pulmonary fibrosis, Usual interstitial pneumonia, Cryptogenic fibrosing alveolitis, Therapy, Azathioprine, Steroids, Glucocorticoids
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Thorax National InstituteOther government
- Collaborators
- Sociedad Chilena de Enfermedades Respiratorias, Servicio de Salud Metropolitano Oriente, Ministerio de Salud de Chile
- Study start
- May 2005
- Study completion
- Dec 2008 (estimated)
- First posted
- 20 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 100.000 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.
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 (P(A-a)O2) 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 CD4/CD8 ratio.
- Transbronchial biopsy.
- Surgical lung biopsy:
- Number
- Site/Side
- 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 ATS/ERS consensus committee (3), and/or with a biopsy proven histological pattern of UIP, will be selected to the randomization process, after they have signed the written informed consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0 | Placebo comparator | Drug: PlaceboPlacebo |
| 1 | Active comparator | Drug: AZAPREDAzathiprine Prednisone |
Who may qualify
- Ages
- 45 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 45 and 79 years of age.
- Clinical symptoms of IPF for at least 3 months.
- Forced vital capacity (FVC) between 50 to 90% of the predicted value.
- DLco at least 35% of the predicted value.
- PaO2 > 55 mm Hg while breathing ambient air at rest.
Key exclusion criteria (22 listed)
- Clinically significant exposure to known fibrogenic agents (birds, molds, hot tubes, asbestos, radiation and drugs known to cause pulmonary fibrosis (amiodarone, nitrofurantoin, bleomicin,etc)).
- History of neurofibromatosis, Hermansky-Pudlak syndrome, metabolic storage disorders, etc.
- History of fever, weight loss, myalgias, arthralgias, skin rash, arthritis.
- Active infection within one week before enrollment.
- Alternative cause of interstitial lung disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo | Drug | 0 |
| AZAPREDThe initial dose of prednisone will be 0.5 mg/kg/day for 4 weeks, then 0.25 mg/kg/day for 8 weeks. The dose will continue to decrease at a rate of 5 to 10 mg per week, to a dose of 0.25 or 0.125 mg/kg/day. Azathioprine will be given at a dose of 2-3 mg/kg/day (max 100 mg). | Drug | 1 |
Primary outcome
Progression-free survival, defined as free of death or a decrease from baseline in the FVC of at least 10%.
Time frame: 2 years
12 secondary outcomes
Number of Acute Exacerbations of IPF.
Time frame: 2 years
Health Related Quality of life, measured with the Chronic Questionnaire (CRQ).
Time frame: 2 years
PO2 at rest and at exercise from baseline.
Time frame: 2 years
P(A-a)O2 at rest and at exercise from baseline.
Time frame: 2 years
Predicted FEV1 from baseline.
Time frame: 2 years
Forced expiratory volume in one second (FEV1) to FVC from baseline.
Time frame: 2 years
Plethysmographic lung volumes from baseline.
Time frame: 2 years
Diffusion capacity for carbon monoxide (DLco) from baseline.
Time frame: 2 years
Six-Minute Walk test, from baseline: resting and 6 minute SpO2, presence or absence of desaturation to 88% or lower at the end of the six minute walk, walked distance d. Pre and post modified Borg dyspnea scores
Time frame: 2 years
Scoring of extent of lung fibrosis on HRCT, according to two independent chest radiologists, form baseline.
Time frame: 2 years
Number and severity of adverse effects.
Time frame: 2 years
Number of protocol drop outs.
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2007.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alvaro Undurraga, MD contact
Florenzano Matías, MD principal investigator
Clínica Las Condes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AZAPRED in people with Idiopathic Pulmonary Fibrosis, run by Thorax National Institute at 1 site in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matias Florenzano, MD (056 9 8294435, mflorenzano@terra.cl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival, defined as free of death or a decrease from baseline in the FVC of at least 10%. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2007.