FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD

Research output: Contribution to journalArticlepeer-review

Authors

  • James Crapo
  • Abhya Gupta
  • David A. Lynch
  • Jens Vogel-Claussen
  • Henrik Watz
  • Robert M. Mroz
  • Wim Janssens
  • Andrea Ludwig-Sengpiel
  • Markus Beck
  • Bérengère Langellier
  • Carina Ittrich
  • Frank Risse
  • Claudia Diefenbach

Colleges, School and Institutes

Abstract

Introduction
A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD, and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS® study (Study 352.2069; NCT02719184) aims to identify biomarkers associated with emphysema, over a 3-year period.

Methods and analysis
The FOOTPRINTS® study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease [GOLD] strategy report), patients with COPD across the GOLD stages 1 to 3, and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (computed tomography and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models.

Ethics and dissemination
The study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, United Kingdom and the United States; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications.

Trial registration number
NCT02719184.

Strengths and limitations of this study
•The study helps to address an unmet need to understand different COPD phenotypes, and to expand on our understanding of biomarkers that are associated with emphysema, and hence COPD, in a 3-year longitudinal setting.
•A subset of patients with alpha1-antitrypsin deficiency provides information on an important but rarely studied subpopulation of patients that present with earlier onset and faster progression of emphysema.
•A regular sampling schedule is employed, with frequent visits and biomarker sample collections to allow early detection of changes, if present.
•Magnetic resonance imaging and sputum collection only occur at certain study sites, and not necessarily at all planned times; hence, the smaller subsets of patients may not be representative of the entire population.
•Patients with the newly defined PRISm phenotype are not included, nor are current smokers or healthy subjects who have never smoked, thus limiting the control groups for reference.

Bibliographic note

Funding: This study was funded and sponsored by Boehringer Ingelheim. The trial clinical monitor for this study was Markus Beck (Boehringer Ingelheim Pharma GmbH & Co. KG, Department of Clinical Research Germany/Respiratory Diseases, Birkendorfer Str. 65, 88 397 Biberach an der Riss, Germany; Phone: +49 (0) 7351/54 96 803).

Details

Original languageEnglish
Article numbere042526
JournalBMJ open
Volume11
Issue number3
Early online date22 Mar 2021
Publication statusE-pub ahead of print - 22 Mar 2021