Last updated on November 2018

Validation of the Risk Stratification Score in Idiopathic Pulmonary Fibrosis


Brief description of study

Idiopathic pulmonary fibrosis (IPF) is a progressing scarring disease of the lungs with an average survival of only 30-36 months since the time of diagnosis. The clinical course of IPF is highly variable, with some patients remaining stable for a prolonged period of time, even in the absence of medical treatment, while others experience rapid and relentless progression. In some cases, the clinical course consists of a stepwise rather than steady decline, with periods of stability alternating with acute respiratory worsening. The variability in clinical course makes it challenging to define prognosis in these patients and, importantly, to determine the right time window for lung transplantation (LTx) referral, listing and priority status on the waiting list.

The risk stratification score (RISE) is a new staging system for IPF based on the MRC dyspnea score, on physiology variables (pulmonary function tests) captured in the Composite Physiologic Index (CPI), and on the 6-minute walk distance. RISE showed to predict survival in newly diagnosed patients with IPF better than any other individual clinical, functional or radiographic variable. RISE also predicted survival on the waiting list in patients assessed and listed for LTx.

Detailed Study Description

The objective of this study is to validate the RISE as a reliable tool to predict survival in patients newly diagnosed with IPF and prospectively followed for a period of 3 years, or until death or lung transplant.

This is an observational, prospective cohort study.

Inclusion criteria will be:

  • a new diagnosis of IPF based on the American Thoracic Society/European Respiratory Society criteria (Am J Respir Crit Care Med 2011;183:788-824) and based on multi-disciplinary discussion with Chest Radiologist and, when a biopsy is available, Lung Pathologist.
  • a pattern consistent with UIP/IPF will be further confirmed by at least 2 expert radiologists, unless a surgical lung biopsy is available.

Exclusion criteria:

  • diagnosis of ILD other than IPF.
  • not a new diagnosis of IPF.

Patients newly diagnosed with IPF will be included in the study.

Patients will be reassessed at 4 months intervals and at each visit the MRC dyspnea score (MRCDS), pulmonary function tests (FEV1, FVC and DLCO), and 6-minute walk distance (6MWD) will be recorded. The RISE will be calculated ad described in Eur Respir J 2012;40:101-109.

MRCDS, PFTs and 6MWD are part of the standard of care in IPF and are routinely obtained at each visit of IPF patients in the ILD clinic (typically every 4 months).

All relevant comorbidities (cardio-vascular disease, diabetes, sleep apnea, chronic obstructive pulmonary disease) will be taken into consideration.

A 2nd HRCT will be repeated at 24 months from the time of diagnosis, or sooner if clinically indicated.

All protocol violations will be recorded.

Patients will be prospectively followed for a period of at least 3 years and mortality events will be recorded. Three-year survival will be the primary endpoint.

Acute exacerbations (AEs) of IPF, as defined in AJR Am J Roentgenol 1997;168:79-83, will also be recorded. AEs will be the secondary endpoint. At the end of the study period, both baseline RISE and longitudinal changes of RISE will be tested as predictors of mortality. Other individual variables will also be tested as predictors of mortality including age at the time of diagnosis, time between onset of symptoms and diagnosis (months), gender, body mass index, smoking history (pack-years), PFTs, 6MWD (meters and % predicted), and radiographic fibrosis score on high resolution chest CT scan (HRCT) at the time of diagnosis.

Values will expressed as meanSD. Comparisons between survivors and non-survivors will be made with unpaired t-test or with the Mann-Whitney U-test, where appropriate. The optimal cut-off value for different variables to detect mortality or AE will assessed using receiver operating characteristics (ROC) analysis. Survival will evaluated using Kaplan-Meier curves and the log-rank test. Cox proportional hazards regression analysis will used to identify significant variables predicting survival status. Results will be summarized as hazard ratios, representing the relative risk of dying as a result of a specific characteristic during the observation period. Variables selected via univariate analysis (p<0.05) will evaluated in the multivariate Cox regression analysis. p-values <0.05 will regarded as significant.

Clinical Study Identifier: NCT02632123

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