Validation of the Risk Stratification Score in Idiopathic Pulmonary Fibrosis

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ClinicalTrials.gov Identifier: NCT02632123

Recruitment Status : Recruiting

First Posted : December 16, 2015

Last Update Posted : August 19, 2019

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Sponsor:

Information provided by (Responsible Party):

Marco Mura, Lawson Health Research Institute

Study Description

Brief Summary:

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.

Condition or disease
Idiopathic Pulmonary Fibrosis

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Detailed 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 and MDD confirms a diagnosis of IPF.

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. 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 (every 4 months).

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

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

Enrollment in pulmonary rehabilitation physiotherapy will be considered and recorded. The length of the enrollment will be considered.

Hospital admission for respiratory reasons will be considered and recorded.

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 lung transplant-free 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 a secondary endpoint.

Progression of disease will be defined as either: >10% absolute reduction in forced vital capacity (FVC) % pred; >50 m decline in 6-minute walk distance (6MWD); admission to hospital for respiratory causes; lung transplantation assessment; or death Progression of disease will be a secondary endpoint.

Patients who received a lung transplant will be censored.

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), radiographic fibrosis score on high resolution chest CT scan (HRCT) at the time of diagnosis; Gender-Age-Physiology (GAP) Index (Ann Intern Med 2012;156:684-691) and Composite Physiologic Index (Am J Respir Crit Care Med 2033;167:962-969).

Values will expressed as mean±SD. 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.

Variance inflation factors of variables predicting endpoint will be calculated to rule out the possibility of multicollinearity and demonstrate that the variables are truly independent.

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.

Areas under the curve (AUC) were compared according to the methods of DeLong et al. (Biometrics 188;44:837-845).

Fine-Gray competing risk regression analysis will be used to account for the competing risks of lung transplant and death (J Am Stat Assoc 1999;94:496-509). p-values <0.05 will regarded as significant.

Study Design

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Study Type :	Observational
Estimated Enrollment :	500 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Validation of the Risk Stratification Score in Idiopathic Pulmonary Fibrosis
Actual Study Start Date :	December 2015
Estimated Primary Completion Date :	December 2022
Estimated Study Completion Date :	December 2022

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Idiopathic pulmonary fibrosis

MedlinePlus related topics: Pulmonary Fibrosis

Genetic and Rare Diseases Information Center resources: Idiopathic Pulmonary Fibrosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Idiopathic pulmonary fibrosis Patients newly diagnosed with idiopathic pulmonary fibrosis

Outcome Measures

Primary Outcome Measures :

Survival [ Time Frame: 3 years ]
Primary outcome is 3-year survival since the time of diagnosis

Secondary Outcome Measures :

Acute exacerbation of IPF [ Time Frame: 3 years ]
Secondary outcome is the incidence of acute exacerbations since the time of diagnosis
Clinical progression [ Time Frame: 3 years ]
Time to either: decline of FVC >10% pred; decline of 6-min walk distance >50 m; hospitalization for respiratory causes; lung transplant assessment; or death.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients newly diagnosed with idiopathic pulmonary fibrosis.

Criteria

Inclusion Criteria:

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 confirmed by a panel of expert chest radiologists.

Exclusion Criteria:

Interstitial lung disease other than IPF

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02632123

Contacts

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Contact: Marco Mura, MD, PhD	+1-5196676744	marco.mura@lhsc.on.ca

Locations

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Canada, Ontario
London Health Science Centre	Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Marco Mura, MD, PhD +15196676744 marco.mura@lhsc.on.ca
Contact: Karishma Hosein +15196858500 ext 55749 karishma.hosein@lhsc.on.ca
Principal Investigator: Marco Mura, MD, PhD

Sponsors and Collaborators

Lawson Health Research Institute

More Information

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Responsible Party:	Marco Mura, Associated Scientist, Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT02632123
Other Study ID Numbers:	10010803
First Posted:	December 16, 2015 Key Record Dates
Last Update Posted:	August 19, 2019
Last Verified:	August 2019

Keywords provided by Marco Mura, Lawson Health Research Institute:


idiopathic pulmonary fibrosis outcome prognosis survival

Additional relevant MeSH terms:

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Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis Pathologic Processes	Lung Diseases Respiratory Tract Diseases Idiopathic Interstitial Pneumonias Lung Diseases, Interstitial

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