Azathioprine and Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis

NCT00518310 | Unknown DMC

• 1 other identifier: 10351
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Interstitial lung disease; Idiopathic pulmonary fibrosis; Usual interstitial pneumonia; Cryptogenic fibrosing alveolitis; Therapy; Azathioprine; Steroids; Glucocorticoids; Corticosteroids; Prednisone

Outcome Measures

Primary Outcomes (1)

• Progression-free survival, defined as free of death or a decrease from baseline in the FVC of at least 10%.

  2 years

Secondary Outcomes (12)

• Number of Acute Exacerbations of IPF.

  2 years

• Health Related Quality of life, measured with the Chronic Questionnaire (CRQ).

  2 years

• PO2 at rest and at exercise from baseline.

  2 years

• P(A-a)O2 at rest and at exercise from baseline.

  2 years

• Predicted FEV1 from baseline.

  2 years

Study Arms (2)

0

PLACEBO COMPARATOR

Placebo

Drug: Placebo

1

ACTIVE COMPARATOR

Azathiprine Prednisone

Drug: AZAPRED

Interventions

Placebo DRUG

0

AZAPRED DRUG

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).

1

Eligibility Criteria

• Age: 45 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thorax National Institute: lead
• Sociedad Chilena de Enfermedades Respiratorias: collaborator
• Servicio de Salud Metropolitano Oriente, Ministerio de Salud de Chile: collaborator

Study Sites (1)

Instituto Nacional del Tórax

Santiago, RM, Chile

RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Florenzano Matías, MD

  Clínica Las Condes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matias Florenzano, MD

CONTACT

056 9 8294435; mflorenzano@terra.cl

Alvaro Undurraga, MD

CONTACT

aundurragap@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: August 16, 2007
• First Posted: August 20, 2007
• Study Start: May 1, 2005
• Study Completion: December 1, 2008
• Last Updated: August 20, 2007

Record last verified: 2007-08

Locations

CL (1)