Clinical trial NCT03591562: Imaging Progression of Chronic Obstructive Pulmonary Disease Using MRI and CT (MR-COPDII)
Official title: Imaging Disease Progression in COPD (MR-COPDII)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: MRI
COPD
Disease Progression
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: Philipps University Marburg
name: Hannover Medical School
name: German Center for Lung Research
First posted: 2018-07-19
Enrollment: 252
Sex: ALL
Minimum age (years): 40
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The trial is fully embedded in the COSYCONET cohort and will only comprise participants of the precursor trial performed between 2013 and 2016:Image-Based Structural and Functional Phenotyping of the COSYCONET Cohort Using MRI and CT (MR-COPD), NCT 02629432.

Brief summary: In this follow-up trial, MRI and CT images of the lung will be acquired prospectively in a subcohort of 370 patients, three years after they successfully participated in the first COSYCONET subtrial with CT and MRI ("MR-COPD I", NCT (clinical.Trials.gov identifier) 02629432).

The objective is to obtain longitudinal data from a well-characterized collective of COPD patients in order to identify suitable image-based biomarkers to improve the prognosis of disease progression of COPD in comparison to clinical tests

Detailed description: There is evidence that both computed tomography (CT) and proton magnetic resonance imaging (1H-MRI) have the potential to detect changes in lung structure and function earlier and with higher sensitivity than currently available clinical tests. We state the hypothesis that the progression of regional lung alterations as detected with MRI and CT precedes the worsening of airflow limitation and clinical symptoms. Before the method can be recommended for patient stratification or for monitoring disease progression, final proof is needed that any changes over time correlate with clinical symptoms and that the quantitative parameters and biomarkers obtained with imaging are predictive for the further course of the disease. Therefore, a dedicated prospective longitudinal trial is required.

The primary end point of the study is to use changes in lung perfusion MRI (e.g. pulmonary blood volume, pulmonary blood flow) and CT (e.g. airway wall thickness, extent of emphysema, extent of air trapping) within a 3-year interval for the prediction of long-term disease progression as monitored by clinical tests (within the following 3 years; BODE index (BODE= body-mass index, airflow obstruction, dyspnea and exercise capacity index in chronic obstructive pulmonary disease). A progression of the disease is defined as an increase of the multidimensional 10-point BODE index by at least one point.

This is an exploratory study. The local two-sided type-I error rate is set to 5%.

Statistical analysis will be primarily conducted as a complete case analysis. Logistic regression models with dependent variable COPD progression will be used. Imaging biomarkers are used as independent variables. All models are adjusted for the prognostic factors age, sex, GOLD (GOLD= Global Initiative For Chronic Obstructive Lung Disease) stage and smoking status as well as the factor study center.

Eligibility criteria: Inclusion Criteria:

* Patients enrolled into the COSYCONET main cohort (Impact of Systemic Manifestations/Comorbidities on Clinical State, Prognosis, Utilisation of Health care resources in Patients with COPD (COSYCONET), NCT01245933), having already successfully participated in the COSYCONET subtrial with CT and MRI performed between December 2013 and July 2016 (Image-Based Structural and Functional Phenotyping of the COSYCONET Cohort Using MRI and CT (MR-COPD), NCT 02629432)

Exclusion Criteria:

* Insufficient quality of MRI and CT obtained at baseline (MR-COPD I)
* Having undergone lung surgery (e.g. lung volume reduction, lung transplantation)
* Moderate or severe exacerbation requiring antibiotic treatment within prior to appointment
* Absence of consent
* Inability to understand the intention of the project
* Contraindications to MRI and/or CT

Primary outcomes:
measure: Sensitivity and specificity of pulmonary blood flow calculated from first pass perfusion MRI to predict disease progression in COPD
timeFrame: Baseline: December 2013-July 2016 Follow-Up: November 2017-June 2020
measure: Sensitivity and specificity of pulmonary blood volume calculated from first pass perfusion MRI to predict disease progression in COPD
timeFrame: Baseline: December 2013-July 2016 Follow-Up: November 2017-June 2020
measure: Sensitivity and specificity of visual perfusion deficit on first pass perfusion MRI to predict disease progression in COPD
timeFrame: December 2013-July 2016 Follow-Up: November 2017-June 2020
measure: Sensitivity and specificity of airway wall metrics on CT to predict disease progression in COPD
timeFrame: Baseline: December 2013-July 2016 Follow-Up: November 2017-June 2020
measure: Sensitivity and specificity of emphysema quantification with CT to predict disease progression in COPD
timeFrame: Baseline: December 2013-July 2016 Follow-Up: November 2017-June 2020
measure: Sensitivity and specificity of air trapping on expiratory CT to predict disease progression in COPD
timeFrame: Baseline: December 2013-July 2016 Follow-Up: November 2017-June 2020
Secondary outcomes:
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH,Klinik für Diagnostische und Interventionelle Radiologie
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Institut für Diagnostische Radiologie u. Neuroradiologie
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf, Pneumologisches Forschungsinstitut
city: Hamburg
country: Germany
facility: Hamburger Institut für Therapieforschung (HIT) GmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Zentrum Radiologie, Institut für Diagnostische und Interventionelle Radiologie
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg, Diagnostische und Interventionelle Radiologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein, Klinik für Diagnostische Radiologie, Campus Kiel
city: Marburg
country: Germany
facility: Universitätsklinikum, Zentrum für Radiologie, Klinik für Diagnostische und Interventionelle Radiologie
city: Muenchen
country: Germany
facility: Klinikum der Universität Muenchen, Klinik und Poliklinik für Radiologie
city: Nuernberg
country: Germany
facility: Klinikum Nord-Nuernberg, Radiologie
Study officials:
affiliation: University Hosital Heidelberg
name: Juergen Biederer, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Heidelberg
name: Bertram J. Jobst, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biederer J, Mirsadraee S, Beer M, Molinari F, Hintze C, Bauman G, Both M, Van Beek EJ, Wild J, Puderbach M. MRI of the lung (3/3)-current applications and future perspectives. Insights Imaging. 2012 Aug;3(4):373-86. doi: 10.1007/s13244-011-0142-z. Epub 2012 Jan 15.
citation: Biederer J, Beer M, Hirsch W, Wild J, Fabel M, Puderbach M, Van Beek EJ. MRI of the lung (2/3). Why ... when ... how? Insights Imaging. 2012 Aug;3(4):355-71. doi: 10.1007/s13244-011-0146-8. Epub 2012 Feb 13.
citation: Wild JM, Marshall H, Bock M, Schad LR, Jakob PM, Puderbach M, Molinari F, Van Beek EJ, Biederer J. MRI of the lung (1/3): methods. Insights Imaging. 2012 Aug;3(4):345-53. doi: 10.1007/s13244-012-0176-x. Epub 2012 Jun 13.
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citation: Gietema HA, Muller NL, Fauerbach PV, Sharma S, Edwards LD, Camp PG, Coxson HO; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Quantifying the extent of emphysema: factors associated with radiologists' estimations and quantitative indices of emphysema severity using the ECLIPSE cohort. Acad Radiol. 2011 Jun;18(6):661-71. doi: 10.1016/j.acra.2011.01.011. Epub 2011 Mar 9.
citation: Karch A, Vogelmeier C, Welte T, Bals R, Kauczor HU, Biederer J, Heinrich J, Schulz H, Glaser S, Holle R, Watz H, Korn S, Adaskina N, Biertz F, Vogel C, Vestbo J, Wouters EF, Rabe KF, Sohler S, Koch A, Jorres RA; COSYCONET Study Group. The German COPD cohort COSYCONET: Aims, methods and descriptive analysis of the study population at baseline. Respir Med. 2016 May;114:27-37. doi: 10.1016/j.rmed.2016.03.008. Epub 2016 Mar 11.
citation: Jorres RA, Welte T, Bals R, Koch A, Schnoor M, Vogelmeier C. [Systemic manifestations and comorbidities in patients with chronic obstructive pulmonary disease (COPD) and their effect on clinical state and course of the disease--an overview of the cohort study COSYCONET]. Dtsch Med Wochenschr. 2010 Mar;135(10):446-9. doi: 10.1055/s-0030-1249185. Epub 2010 Mar 2. German.