Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment

Overview

The Chronic Hypersensitivity Pneumonitis (HP), is an inflammatory disease who has an evolution to develop progressive interstitial fibrosis, who cause the death of the patient. Actually HP has been treated with Prednisone and occasionally with Azathioprine, but unfortunately the treatment with these drugs have not an effective result to treat the interstitial fibrosis.

Pirfenidone has been studied over the world for the treatment of Fibrotic diseases, with positive results, and due to the Pirfenidone mechanism of action has anti-inflammatory and anti-fibrotic properties, the investigators propose to evaluate the addition of Pirfenidone to the actual treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 2016

Detailed Description

The Chronic Hypersensitivity Pneumonitis (HP), is a complex syndrome due to a exaggerated immune response caused by inhalation of foreign substances, such as molds, dusts, and organic particles, causing alveoli inflammation and in the chronic forms the disease has high rate of mortality, due to the big number of patients who develop progressive interstitial fibrosis and eventually they curse with respiratory insufficiency who cause the death of the patient.

Pirfenidone has been studied over the world for the treatment of Idiophatic Pulmonary Fibrosis (IPF), disease who constitute the most aggressive of the fibrotic diseases of the lung. Additionally Pirfenidone has been showed potential results in the treatment of fibrotic diseases in other organs, as Liver, Kidney, Hearth, etc. Pirfenidone has been described as a modulator of the fibrotic process due to his action over TGF-beta and MMP´s and also has into-inflammatory actions acting over TNF-alfa and IL-1 and IL-6.

Actually HP has been treated with Prednisone and occasionally with Azathioprine, but a high number of patients will develop irreversibly to a interstitial fibrosis with pulmonary parenchyma destruction. Unfortunately the investigators have not an effective treatment for this cases. Due to the positive results obtained with Pirfenidone in the treatment of IPF and other kind of organ fibrosis, the investigators propose to evaluate the addition of Pirfenidone to the treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis.

Interventions

  • Drug: Placebo
    • Placebo tablet only with the excipients of the Pirfenidone tablet
  • Drug: Pirfenidone
    • Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1800 mg
  • Drug: Pirfenidone
    • Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1200 mg

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • Conventional treatment (Prednisone 0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Placebo tablet 2 times at day.
  • Experimental: Pirfenidone 1800 mg
    • Conventional treatment (0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Pirfenidone long release tablet 900 mg 2 times at day, starting with 600 mg at day
  • Experimental: Pirfenidone 1200 mg
    • Conventional treatment (0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Pirfenidone long release tablet 600 mg 2 times at day starting with 600 mg at day

Clinical Trial Outcome Measures

Primary Measures

  • Forced Vital Capacity (FVC)
    • Time Frame: 52 weeks
    • The measurement of FVC will be at 26 and 52 weeks

Secondary Measures

  • High Resolution Tomography
    • Time Frame: 52 weeks
    • Evaluation of the inflammation and fibrosis grade with the Kazerooni scale
  • 6 minutes walk distance test
    • Time Frame: 52 weeks
    • quantification of the walking distance at 6 minutes
  • San George Qty Score, SOBQ and EQ5D Quality Scores
    • Time Frame: 52 weeks
    • As a composite outcome to evaluate the quality of life
  • Pulmonary artery systolic pressure with echocardiogram
    • Time Frame: 52 weeks
    • measurement of pressure
  • Oxygen desaturation in exercise
    • Time Frame: 52 weeks
    • Measurement of Oxygen

Participating in This Clinical Trial

Inclusion Criteria

  • Chronic Hypersensitivity pneumonitis with recent diagnosis confirmed by HRT with or without biopsy
  • Acceptation with signed informed consent

Exclusion Criteria

  • No confirmed diagnosis
  • Patients with peptic ulcer
  • Pregnancy or breast feeding period
  • Clinical signs of active infection
  • History of severe Hepatic disease
  • History of severe Kidney disease, who requires some kind of dialysis
  • History of inestable cardiopathy
  • History of alcohol or drugs abuse
  • Bronchial hyperactivity or History of asthma or EPOC
  • Smoking habit 3 months before the starting or patient who decline suspend the smoking habit during the study
  • Patient with impossibility to make spirometry or who can not walk
  • Use of Immunosuppressants, cytotoxic agents, cytosine modulators or receptor antagonist, fluvoxamine or daily use of sildenafil.
  • Patients who not accept sign the informed consent

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Grupo Medifarma, S. A. de C. V.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Pedro Pena, MD, +52191971972, pedropena@grupomedifarma.com

References

Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y; HP Study Group. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):952-8. Epub 2003 Jul 3.

Selman M. Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med. 2004 Sep;25(3):531-47, vi. Review.

Gaxiola M, Buendía-Roldán I, Mejía M, Carrillo G, Estrada A, Navarro MC, Rojas-Serrano J, Selman M. Morphologic diversity of chronic pigeon breeder's disease: clinical features and survival. Respir Med. 2011 Apr;105(4):608-14. doi: 10.1016/j.rmed.2010.11.026. Epub 2010 Dec 16.

Macías-Barragán J, Sandoval-Rodríguez A, Navarro-Partida J, Armendáriz-Borunda J. The multifaceted role of pirfenidone and its novel targets. Fibrogenesis Tissue Repair. 2010 Sep 1;3:16. doi: 10.1186/1755-1536-3-16.

Selman M, Pardo A, Richeldi L, Cerri S. Emerging drugs for idiopathic pulmonary fibrosis. Expert Opin Emerg Drugs. 2011 Jun;16(2):341-62. doi: 10.1517/14728214.2011.565049. Epub 2011 Mar 17. Review.

Schaefer CJ, Ruhrmund DW, Pan L, Seiwert SD, Kossen K. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev. 2011 Jun;20(120):85-97. doi: 10.1183/09059180.00001111. Review.

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