Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2007 by Thorax National Institute.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Sociedad Chilena de Enfermedades Respiratorias
Servicio de Salud Metropolitano Oriente, Ministerio de Salud de Chile
Information provided by:
Thorax National Institute
ClinicalTrials.gov Identifier:
NCT00518310
First received: August 16, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

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.


Condition Intervention
Idiopathic Pulmonary Fibrosis
Drug: Placebo
Drug: AZAPRED

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis: a Randomized, Double-Blind, Controlled Study

Resource links provided by NLM:


Further study details as provided by Thorax National Institute:

Primary Outcome Measures:
  • Progression-free survival, defined as free of death or a decrease from baseline in the FVC of at least 10%. [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 100
Study Start Date: May 2005
Estimated Study Completion Date: December 2008
Arms Assigned Interventions
Placebo Comparator: 0
Placebo
Drug: Placebo
Active Comparator: 1
Azathiprine Prednisone
Drug: AZAPRED
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).

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  Eligibility

Ages Eligible for Study:   45 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518310

Contacts
Contact: Matias Florenzano, MD 056 9 8294435 mflorenzano@terra.cl
Contact: Alvaro Undurraga, MD aundurragap@yahoo.com

Locations
Chile
Instituto Nacional del Tórax Recruiting
Santiago, RM, Chile
Contact: Jeannie Hinrichsen, RN       jhinrichsen@torax.cl   
Contact: Carmen L Naranjo       cnaranjo@torax.cl   
Principal Investigator: Florenzano Matias, MD         
Principal Investigator: Undurraga Alvaro, MD         
Sub-Investigator: Juan C Rodríguez, MD         
Sub-Investigator: Jorge Navarro, MD         
Sub-Investigator: Carlos Inzunza, MD         
Sub-Investigator: Mariam Torres, Ph         
Sub-Investigator: Eduardo Sabbagh, MD         
Sub-Investigator: Juan C Díaz, MD         
Sub-Investigator: Gabriel Cavada, Stat         
Sponsors and Collaborators
Thorax National Institute
Sociedad Chilena de Enfermedades Respiratorias
Servicio de Salud Metropolitano Oriente, Ministerio de Salud de Chile
Investigators
Principal Investigator: Florenzano Matías, MD Clínica Las Condes
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00518310     History of Changes
Other Study ID Numbers: 10351
Study First Received: August 16, 2007
Last Updated: August 16, 2007
Health Authority: Chile: Comité Ético-Científico Servicio de Salud Metropolitano Oriente

Keywords provided by Thorax National Institute:
Interstitial lung disease
Idiopathic pulmonary fibrosis
Usual interstitial pneumonia
Cryptogenic fibrosing alveolitis
Therapy
Azathioprine
Steroids
Glucocorticoids
Corticosteroids
Prednisone

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Azathioprine
Prednisone
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on August 26, 2014