Clinical trial NCT04140097: Predictors of Acute Exacerbation in Patients With COPD - an Observational Study
Official title: Predictors of Acute Exacerbation in Patients With COPD - an Observational Study (PACE Trial)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Chronic Obstructive Pulmonary Disease
COPD
COPD Exacerbation
COPD Exacerbation Acute
Keywords: Predictor
Development
Pulmonary Rehabilitation
Lead sponsor: Schön Klinik Berchtesgadener Land
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline GmbH & Co. KG (Munich, Germany)
name: Coordinating Center for Clinical Trials (KKS; Philipps-University of Marburg, Germany)
name: Research Office (Biostatistics), Paracelsus Medical University (Salzburg, Austria)
name: Fraunhofer ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (Hannover, Germany)
name: Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg (Marburg, Germany)
First posted: 2019-10-25
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline laboratory parameters at day 21
timeFrame: baseline and day 21
measure: Change from day 1 of an acute exacerbation in laboratory parameters at day 5
timeFrame: day 1 and 5 in case of an acute exacerbation
measure: Change from baseline lung function at day 21
timeFrame: baseline and day 21
measure: Change from day 1 of an acute exacerbation in lung function at day 5
timeFrame: day 1 and 5 in case of an acute exacerbation
measure: Change from baseline Cardiac Doppler echocardiography at day 21
timeFrame: baseline and day 21
measure: Change from day 1 of an acute exacerbation in Cardiac Doppler echocardiography at day 5
timeFrame: day 1 and 5 in case of an acute exacerbation
measure: Change from baseline breath volatile organic compounds Analysis to day 4, 8, 11, 15 and 18
timeFrame: day 1, 4, 8, 11, 15, 18
measure: Change in baseline exercise Performance at day 21
timeFrame: day 1 and 21
measure: Change from baseline Quality of life assessed by Short Form - 36 Questionnaire at days 21, day 180, day360, day 720
timeFrame: baseline, day 21, day 180, day 360, day 720
measure: Change from baseline functional status assessed by Modified Medical Research Counsil score at days 21, day 180, day360, day 720
timeFrame: baseline, day 21, day 180, day 360, day 720
measure: Change from baseline anxiety status assessed by Chronic Obstructive Pulmonary Disease Anxiety Questionnaire at days 21, day 180, day360, day 720
timeFrame: baseline, day 21, day 180, day 360, day 720
measure: Change from baseline Depression status assessed by Patient Health Questionnaire 9 at days 21, day 180, day360, day 720
timeFrame: baseline, day 21, day 180, day 360, day 720
measure: Change from baseline disease specific Quality of life assessed by Chronic Obstructive Pulmonary Disease Assessment Test at days 21, day 180, day360, day 720
timeFrame: baseline, (day 1 and 5 in case of an acute exacerbation), day 21, day 180, day 360, day 720
measure: Self-reported patient diary
timeFrame: once daily from day 1 to day 21
measure: physical activity monitoring
timeFrame: continuous monitoring from day 1 to day 21
measure: Change in Survival Status from baseline at 6, 12 and 24 months
timeFrame: baseline, at 6, 12 and 24 months
measure: cough events
timeFrame: Recording from day 1 to day 21 at night only
measure: Self-reported patient symptom diary
timeFrame: Once daily from day 1 to day 21
Secondary outcomes:
Other outcomes:
Locations:
city: Schoenau Am Koenigssee
country: Germany
facility: Schoen Klinik Berchtesgadener Land
Study officials:
References:
citation: 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.