Predictors of Acute Exacerbation in Patients With COPD - an Observational Study (PACE)

Predictors of Acute Exacerbation in Patients With COPD - an Observational Study (PACE Trial)

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by respiratory problems and poor airflow with dyspnea and cough being the main symptoms. Acute exacerbations of COPD (AECOPD) are the most important events for patients with COPD that have a negative impact on patients´ quality of life, accelerate disease progression, and can result in hospital admissions and death. It is of major clinical importance to determine predictors of an AECOPD and to identify patients who are at high risk for developing an acute exacerbation and/or to detect the beginning of or prevent an ongoing acute exacerbation as early as possible. Until now, research in the field of AECOPD has gathered and analyzed data only after manifestation of AECOPD until recovery and most of them used a retrospective study design. Therefore, the aim of this prospective trial is to collect clinical data in patients prior to the first visible clinical signs of an AECOPD to investigate potential early predictors of an AECOPD.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; COPD; COPD Exacerbation; COPD Exacerbation Acute
• Intervention / Treatment: Other: Prospective monitoring of a large variety of parameters

Detailed Description

In total, 355 COPD patients will be included prospectively to this study during a 3-week inpatient pulmonary rehabilitation programme at the Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee, (Germany). All patients will be closely monitored from admission to the study. Measures of lung function, blood samples, breath sampling, exercise tests, physical activity monitoring, cardiac parameters, quality of life and a symptom diary will be recorded regularly. Prior knowledge from this programme suggest that about 15% of patients will develop an AECOPD during this observational phase. If a patient develops an AECOPD there will be a comprehensive diagnostic assessment to differentiate between cardiac, pulmonary or cardio-pulmonary reasons for the AECOPD and to identify the type of exacerbation. The clinical diagnosis and management of an AECOPD will be determined by a pulmonologist according to criteria of international guidelines within the first 24h after the onset of clinical symptoms suggestive of an exacerbation. Collected clinical data from the days prior to AECOPD will be analyzed comprehensively to identify parameters with high prediction power for AECOPD. Furthermore, patients will perform follow-up measures at 6, 12 and 24 months following the initial observational phase (PR phase).

A wide range of predictor screening methods will be applied to identify significant predictors including cross tabulation tables, correlations, generalized linear models, mixed models, generalized estimation equation models and various predictor screening methods based on variable selection algorithms.

Study objectives Primary endpoint: To prospectively identify potential early, respiratory and/ or cardiac clinical predictors, laboratory parameters, breath print analyses and/ or changes in lung function and physical activity prior to an AECOPD in COPD patients.

Secondary endpoint(s):

1. To identify potential mechanisms explaining the nature and composition of an acute exacerbation in COPD patients
2. To identify and differentiate patterns of acute COPD exacerbation versus cardiac failure in COPD patients
3. To investigate the potential role of an electronic-nose to capture exhaled breath metabolomic profiles for the early detection of an acute exacerbation in COPD patients ("COPD pre exacerbation breath print")
4. To identify parameters influencing mortality and other adverse events in the total study cohort at 6, 12 and 24 months follow up

• Study Type: Observational
• Enrollment (Estimated): 355

Contacts and Locations

• Study Contact: Name: Rainer Gloeckl, PhD; Phone Number: +49-8652-931630; Email: rgloeckl@schoen-klinik.de

Study Locations

• Germany
  • Schoenau Am Koenigssee, Germany, 83471
    • Recruiting
    • Schoen Klinik Berchtesgadener Land
    • Contact: Rainer Gloeckl, PhD; Phone Number: 08652-931630; Email: rgloeckl@schoen-klinik.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Chronic Obstructive Pulmonary Disease that are referred to an inpatient pulmonary rehabilitation program at the reference center.

Description

Inclusion Criteria:

• confirmed diagnosis of Chronic Obstructive Pulmonary Disease according to Global Association for Obstructive Lung Disease stage II to IV
• the ability to follow the rehabilitation protocol
• provided written informed consent

Exclusion Criteria:

- current primary diagnosis of asthma

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COPD patients with acute exacerbation	Other: Prospective monitoring of a large variety of parameters; Patients will be recruited during an inpatient pulmonary rehabilitation program. This setting offers a unique opportunity to study the phenomenon of an acute exacerbation of the Chronic Obstructive Pulmonary Disease prior to the first visible clinical sign and further on to have a follow up of the underlying mechanisms. All COPD patients that are referred to the reference center for a rehabilitation program will be included after providing written informed consent. Prospectively, a wide range of measurements will be collected. If a patient develops an acute exacerbation there will be a comprehensive diagnostic assessment to differentiate between pulmonary, cardiac or cardio-pulmonary reasons for the exacerbation. The clinical diagnosis of an AECOPD will be made by a pulmonologist according to criteria of international guidelines within the first 24h of clinical symptoms suggestive of an exacerbation.
COPD patients without acute exacerbation	Other: Prospective monitoring of a large variety of parameters; Patients will be recruited during an inpatient pulmonary rehabilitation program. This setting offers a unique opportunity to study the phenomenon of an acute exacerbation of the Chronic Obstructive Pulmonary Disease prior to the first visible clinical sign and further on to have a follow up of the underlying mechanisms. All COPD patients that are referred to the reference center for a rehabilitation program will be included after providing written informed consent. Prospectively, a wide range of measurements will be collected. If a patient develops an acute exacerbation there will be a comprehensive diagnostic assessment to differentiate between pulmonary, cardiac or cardio-pulmonary reasons for the exacerbation. The clinical diagnosis of an AECOPD will be made by a pulmonologist according to criteria of international guidelines within the first 24h of clinical symptoms suggestive of an exacerbation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline laboratory parameters at day 21	following Parameters will be collected: c-reactive protein, cardiac Troponin I, hemoglobin A1c, Interleukin-1 beta, Interleukin-2, Interleukin-6, Interleukin 8, N-terminal probrain natriuretic peptide, Tumor necrosis factor alpha	baseline and day 21
Change from day 1 of an acute exacerbation in laboratory parameters at day 5	following Parameters will be collected: c-reactive protein, cardiac Troponin I, hemoglobin A1c, Interleukin-1 beta, Interleukin-2, Interleukin-6, Interleukin 8, N-terminal probrain natriuretic peptide, Tumor necrosis factor alpha	day 1 and 5 in case of an acute exacerbation
Change from baseline lung function at day 21	following Parameters will be collected: forced expiratory volume in 1 sec, forced vital capacity, total lung capacity, residual volume	baseline and day 21
Change from day 1 of an acute exacerbation in lung function at day 5	following Parameters will be collected: forced expiratory volume in 1 sec, forced vital capacity, total lung capacity, residual volume	day 1 and 5 in case of an acute exacerbation
Change from baseline Cardiac Doppler echocardiography at day 21	Left and right heart echocardiography will be performed	baseline and day 21
Change from day 1 of an acute exacerbation in Cardiac Doppler echocardiography at day 5	Left and right heart echocardiography will be performed	day 1 and 5 in case of an acute exacerbation
Change from baseline breath volatile organic compounds Analysis to day 4, 8, 11, 15 and 18	breath samples will be analyzed by ion-mobility spectrometry and gaschromatography/mass spectrometry	day 1, 4, 8, 11, 15, 18
Change in baseline exercise Performance at day 21	following tests will be performed: 6-Minute walk test, sit-to-stand-test, Peak quadriceps and Hand grip force,	day 1 and 21
Change from baseline Quality of life assessed by Short Form - 36 Questionnaire at days 21, day 180, day360, day 720	the scale of the physical and mental Health component summary score ranges from 0 to 100 Points with higher scores indicating better Quality of lif	baseline, day 21, day 180, day 360, day 720
Change from baseline functional status assessed by Modified Medical Research Counsil score at days 21, day 180, day360, day 720	the score ranges from category 0 to 4 with higher scores indicating higher impairment in function status	baseline, day 21, day 180, day 360, day 720
Change from baseline anxiety status assessed by Chronic Obstructive Pulmonary Disease Anxiety Questionnaire at days 21, day 180, day360, day 720	the total score ranges from 0 to 112 Points with higher scores indicating worse anxiety status	baseline, day 21, day 180, day 360, day 720
Change from baseline Depression status assessed by Patient Health Questionnaire 9 at days 21, day 180, day360, day 720	the total score ranges from 0 to 27 Points with higher scores indicating worse Depression symptoms	baseline, day 21, day 180, day 360, day 720
Change from baseline disease specific Quality of life assessed by Chronic Obstructive Pulmonary Disease Assessment Test at days 21, day 180, day360, day 720	total score ranges from 0 to 40 points with higher scores indicating worse quality of life	baseline, (day 1 and 5 in case of an acute exacerbation), day 21, day 180, day 360, day 720
Self-reported patient diary	The EXAcerbations of Chronic pulmonary disease Tool will be used	once daily from day 1 to day 21
physical activity monitoring	Using the Actigraph device following Parameters will be collected: steps per day and physical activity levels	continuous monitoring from day 1 to day 21
Change in Survival Status from baseline at 6, 12 and 24 months	Survival Status will be assessed by phone calls	baseline, at 6, 12 and 24 months
cough events	Number of nocturnal cough events recorded by NELA sound device (Carepath)	Recording from day 1 to day 21 at night only

Collaborators and Investigators

• Sponsor: Schön Klinik Berchtesgadener Land
• Collaborators: GlaxoSmithKline GmbH & Co. KG (Munich, Germany); Coordinating Center for Clinical Trials (KKS; Philipps-University of Marburg, Germany); Research Office (Biostatistics), Paracelsus Medical University (Salzburg, Austria); Fraunhofer ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (Hannover, Germany); Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg (Marburg, Germany)

Publications and helpful links

General Publications

• Kenn K, Gloeckl R, Leitl D, Schneeberger T, Jarosch I, Hitzl W, Alter P, Sczepanski B, Winterkamp S, Boensch M, Schade-Brittinger C, Skevaki C, Holz O, Jones PW, Vogelmeier CF, Koczulla AR. Protocol for an observational study to identify potential predictors of an acute exacerbation in patients with chronic obstructive pulmonary disease (the PACE Study). BMJ Open. 2021 Feb 8;11(2):e043014. doi: 10.1136/bmjopen-2020-043014.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Rehabilitation; Development; Predictor
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: PACE Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No