The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trialReport as inadecuate

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Respiratory Research

, 12:93

First Online: 01 December 2011Received: 03 February 2011Accepted: 15 July 2011


BackgroundOur phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis IPF revealed the efficacy in reducing the decline of vital capacity VC and increasing the progression-free survival PFS time by pirfenidone. Recently, marginal decline in forced VC FVC has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC.

MethodsImprovement ratings based on 5% change in absolute VC, i.e. -improved VC ≥ 5% increase- -stable VC < 5% change-, and -worsened VC ≥ 5% decrease- at month 3, 6, 9 and 12 were compared between high-dose pirfenidone 1800 mg-day; n = 108 and placebo n = 104 groups, and high-dose and low-dose 1200 mg-day; n = 55 pirfenidone n = 163 and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering -worsened- and -non-worsened improved and stable- of the ratings at months 3 and 12 as -positive- and -negative-, respectively, and the positive and negative predictive values of the ratings were calculated in each group.

ResultsIn the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive-negative predictive values in placebo and pirfenidone groups were 86.1%-50.8% and 87.1%-71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year.

ConclusionsThe efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF.

Trial RegistrationThis clinical trial was registered with the Japan Pharmaceutical Information Center JAPIC on September 13, 2005 Registration Number: JAPICCTI-050121.

Abbreviations used in this paperIPFidiopathic pulmonary fibrosis

VCvital capacity

FVCforced vital capacity

TLCtotal lung capacity

PaO2alveolar-arterial oxygen tension

PFSprogression-free survival

SpO2oxygen saturation by pulse oximetry

DLCOdiffusing capacity for carbon monoxide

FASfull analysis set

PFTpulmonary function test

6MET6-minute steady-state exercise test

SP-A or DSurfactant protein-A or D


BMIBody Mass Index


ATSAmerican Thoracic Society

ERSEuropean Respiratory Society.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-93 contains supplementary material, which is available to authorized users.

Hiroyuki Taniguchi, Yasuhiro Kondoh contributed equally to this work.

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Author: Hiroyuki Taniguchi - Yasuhiro Kondoh - Masahito Ebina - Arata Azuma - Takashi Ogura - Yoshio Taguchi - Moritaka Suga - Hiro


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