Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01949727 |
| Other study ID # |
Pro00038838 |
| Secondary ID |
AIHS-CRIO Projec |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 2013 |
| Est. completion date |
December 2020 |
Study information
| Verified date |
September 2021 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease primarily caused by
smoking. COPD creates a tremendous burden to the healthcare system, as disease exacerbations
result in frequent, prolonged hospitalizations. While originally considered a disease
specific to the lung, data have shown that COPD is associated with substantial cardiovascular
(CV) morbidity and mortality. Exacerbations of COPD requiring hospitalization result in
marked patient deterioration, and heightened CV risk. The cause of the increased CV risk with
stable COPD, and the exaggerated CV risk during exacerbations of the disease are unknown;
however, it may be due to chronic inflammation which is exacerbated with a flare-up of the
disease, and/or chronic inactivity which is similarly worsened with bed-rest during a
hospitalization. Despite the impact of COPD on healthcare, there are relatively few studies
examining how COPD inpatient care impacts on patient outcomes, inflammation and CV risk.
Disease management programs, such as pulmonary rehabilitation and patient self-management
education, are part of guideline therapy for COPD; however, these are not regularly
implemented following a hospitalization, and how these interventions affect patient outcomes,
behavior, physical activity, inflammation and CV risk have not been well studied. The
proposed long-term project will examine how typical inpatient COPD care, and how early
referral to chronic disease management programs after hospital discharge, affect patient
outcomes. This grant brings together an outstanding group of researchers who have the
necessary clinical, content and methodological expertise to successfully complete this work.
These studies will provide invaluable information about inpatient and outpatient management
for a disease which has a tremendous impact on healthcare.
Description:
AIM 1:
Purpose: To examine pulmonary and cardiovascular outcomes in COPD patients from the time of
their acute hospital admission until discharge.
Rationale: AECOPD is associated with systemic inflammation, prolonged bed-rest and increased
CV risk. Proper medical management strategies such as appropriate systemic corticosteroids,
mobilization, and bedside education may reduce systemic inflammation and improve vascular
function, while improving patient self-efficacy and health outcomes and reducing hospital
length of stay (LOS).
Hypothesis: Treatment-specific factors such as pharmacological management, patient education
and inpatient mobilization will affect LOS, as well as pulmonary and cardiovascular outcomes
at discharge.
Study Design: For this cross-sectional study, consecutive patients admitted to the University
of Alberta Hospital Pulmonary ward with a diagnosis of an AECOPD (with BNP <500 pg/ml and
Troponin <1.0 mcg/L), not requiring ventilatory support in the form of non-invasive
ventilation (NIV), will be approached for recruitment. In-hospital patient management will be
left to the discretion of the admitting physician, and will follow the new AHS admission
order sets for AECOPD, which are based on current guidelines1. Dr Bhutani assisted in the
development of these order sets. The order sets standardize pharmacological and
non-pharmacological management of AECOPD; however, variance in patients need and time to
delivery of these interventions will be present. Treatment will not be otherwise altered
during this study, except the timing of the administration of short acting bronchodilators as
it relates to the measurement of arterial stiffness and vascular function. 24 hours after
recruitment, the research team will begin collecting patient/clinical treatment information
on a daily basis (see Appendix B for list). 48 hours after admission, patients will be given
an activity monitor to quantify daily physical activity. On the same day, vascular assessment
through the measurement of pulse wave velocity, vascular function, lung function as well as
serum markers of systemic inflammation (TNF-alpha, MMP-2, IL-6 and CRP) and exhaled nitric
oxide (eNO), will be collected (this is in addition to usual blood work required for patient
management). This will be repeated on days 5, 10, day of discharge and day 14 post discharge.
Self efficacy and a 6-minute walk test will be performed on the day of discharge and on day
14 following discharge, while three-day physical activity will be determined at 14 days post
discharge. BODE index will be determined at discharge and at 14 days post discharge (see
Appendix C for data collection schedule).
Subject Selection & Recruitment: All Aims will be registered at (www.clinicaltrials.gov),
submitted for approval through the University of Alberta Health Research Ethics Board (HREB),
and informed consent will be obtained from each study patient.
Since most of patients with COPD who are hospitalized initially present to, and are assessed
in the Emergency Department (ED), they will be recruited from this setting by the ED study
team. All patients with a diagnosis of AECOPD who are admitted to the pulmonary ward, meeting
the above criteria, will be screened for enrollment. If entered into the study, baseline
information (Appendix A) will be collected at that time. Through collaborative and primary ED
research activity, Dr Rowe's Emergency Medicine Research Group maintains research nurse
coverage for the U of A hospital ED from 07:00 - 23:00 Monday - Friday and 10:00 - 20:00
Saturday and Sunday. These research nurses act as the main recruitment source within the
University of Alberta Hospital ED and this site has been a leading Canadian recruitment
centre in a number of clinical research studies. Eligible patients with AECOPD will be
approached to enter the study as required and informed written consent will be obtained. A
Refused, Missed or Otherwise (RMO) excluded database will be maintained to determine the
feasibility of a larger study and to assess the generalizability of the enrolled sample to
all cases. In the event that a patient presents after research staff hours, the patient will
be approached by the research staff to discuss the study and obtain consent and begin
collection of all data. AHS data indicates that ~450 COPD patients are admitted at the U of A
hospital each year. Dr Rowe's research team has demonstrated success at recruiting through
the ED120,121, and therefore recruiting 100 patients over 2 years is feasible
Data Handling: Upon enrollment a data collection form (Appendix A) will be completed for all
patients by the ED research team. The research team will collect patient/clinical treatment
information daily (see Appendix B), and outcome data per protocol (see Appendix C).
Data Analysis: All data will be entered into a custom-developed secure anonymized database.
Data analyses will be performed using StataCorp. 2009. Stata Statistical Software: Release 11
(College Station, TX: StataCorp LP). Continuous data will be reported as means and standard
deviations (SD) or median and interquartile ranges (IQR). Chi-square testing will be used for
bi-variable analyses of dichotomous variables; continuous variables will be compared using
t-tests or Mann-Whitney tests. Two-tailed results p < 0.05 will be considered statistically
significant. The influence of patient characteristics and treatment factors on the dependent
variables (i.e. inflammation, vascular function, self efficacy and LOS) will analyzed through
a multiple linear or logistic regression models as appropriate. For the linear regression
model, clinically relevant and statistically significant (at the p < 0.1 level) independent
variables will be included. For the logistic regression model, several dependent variables
will be explored; clinically relevant and statistically significant (at the p < 0.1 level)
independent variables will be included.
Sample size: A convenience sample of COPD patients will be recruited and efforts will be made
to provide reasonable confidence intervals on important variables and outcomes; a minimum
sample size of 100 COPD cases will be collected. This will be sufficient for multiple
regression analyses including up to 10 predictors and would provide narrow 95% confidence
intervals (CI) for variable estimates of ~10% for mid-range variables and 6%. for
extreme-range variables.
AIM 2:
Purpose: To examine the impact of early PR following hospital discharge on QoL, pulmonary/CV
outcomes and AECOPD hospitalizations.
Rationale: In addition to typical improvements in QoL and exercise tolerance, studies have
shown that PR increases self-efficacy, physical activity while reducing CV risk in stable
COPD patients. Patients recently discharge from hospital following AECOPD represent the
sickest patients with greatly reduced QoL, exercise tolerance, self-efficacy and physical
activity and greatly elevated CV risk. Exactly how these improve with PR reduce CV risk and
hospitalizations following PR requires examination.
Hypothesis: Patients who receive early PR will have improved QoL, pulmonary/CV outcomes and
less hospitalizations for COPD in the 6 months following hospital discharge. PR will improve
self efficacy, physical activity and QoL while reducing CV risk as compared to usual care.
Study Design & Subject Recruitment: All patients admitted to the pulmonary ward for an
AECOPD, including those who have completed Aim 1, will be offered participation into this arm
of the study. Patients found to have an acute cardiac injury during admission, mobility
issues or residence outside the greater Edmonton area will be excluded. Consenting patients
will be subsequently randomized into one of two groups: early PR versus usual care. Patients
randomized to early PR will be enrolled within 1 month of discharge into a PR program, while
usual care patients will be followed-up by their most responsible physician as determined by
the admitting team. The PR group will be enrolled in the Breathe Easy Program at the Center
for Lung Health, and will proceed through the program in a typical fashion. All patients will
be followed up 6 months after discharge and will be interviewed to assess disease status,
management review and if there has been a history of recurrence or relapse of the AECOPD.
Hospital admissions and length of stay data will be obtained through electronic medical
records. Patient assessments will include: quality of life, 6min walk, dyspnea,
self-efficacy, physical activity, pulse wave velocity, vascular function, systemic
inflammation (TNFα, MMP-2, IL-6 and CRP) and FeNO. All data will be collected before,
immediately after and 6month after PR. The control group will have the same data collected at
the same scheduled time. See above for descriptions of methods.
Data Handling: Data will be entered onto a secure anonymized database.
Data Analysis: The influence of PR on QoL, 6min walk, dyspnea, self-efficacy, physical
activity, pulse wave velocity, vascular function, systemic inflammation and eNO will be
analyzed using a multivariate mixed-model MANOVA with treatment (PR vs. usual care) being a
fixed between-group variable and time (pre, immediate post, 6months post) as a repeated
variable.
Sample size: Based on previous work84,95,96,101-105, a sample size of 50 in each group (100
total) will be sufficient to detect a between-group differences in QoL, 6min walk, PWV,
dyspnea and hospital readmission rates following PR (α=0.05, β=0.8). Based on our recent
work, this sample could detect a 10% difference in physical activity following PR (α=0.05,
β=0.8). One hundred patients will also to allow for stratification of physiological and
psychological responses with PR.
