Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00557115 |
| Other study ID # |
05/Q0703/093 |
| Secondary ID |
BLF PO4/8 |
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 2006 |
| Est. completion date |
April 16, 2008 |
Study information
| Verified date |
November 2007 |
| Source |
King's College Hospital NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The principal aim of the study is to evaluate whether attendance at an exercise training and
education programme (known as pulmonary rehabilitation) shortly following hospital discharge
can lead to a reduction in exacerbations and improvement in exercise capacity and quality of
life in patients with chronic obstructive pulmonary disease.
Description:
Background:
Chronic obstructive pulmonary disease (COPD), also sometimes known as chronic asthma,
bronchitis or emphysema, is an important health problem. Many people with COPD are admitted
into hospital with a worsening of their symptoms, known as an exacerbation. Hospitalisations
for acute exacerbations of chronic obstructive pulmonary disease (COPD) are a massive burden
to the NHS. Over the past decade, these hospitalizations have increased by 50%, and annual
hospital costs for COPD in the UK amount to more than £587 million. After being discharged,
some people fail to cope very well due to a variety of reasons. A prolonged stay in hospital
may lead to muscle weakness, particularly of the leg muscles [1], a loss of confidence in
performing everyday activities, and increased anxiety [2]. A high proportion of these
patients are re-admitted to hospital following discharge. The aim of the study is to assess
whether attendance at an exercise training and education programme shortly following
discharge can firstly, improve exercise capacity and quality of life, and secondly, reduce
the use of health resources and costs to the NHS.
It is known that an exercise training and education programme known as Pulmonary
Rehabilitation is beneficial to stable patients with COPD by reducing breathlessness,
increasing exercise capacity and improving quality of life. We have recently performed a
pilot study that has shown that early Pulmonary Rehabilitation has considerable short-term
benefits in patients with COPD who have been recently discharged following a hospital
admission for worsening of their symptoms [3]. We hypothesise that these benefits are
long-lasting, and may reduce use of healthcare resources and costs to the NHS.
References:
1. Spruit, M.A., et al., Muscle force during an acute exacerbation in hospitalised patients
with COPD and its relationship with CXCL8 and IGF-I. Thorax, 2003. 58(9): p. 752-6.
2. Seemungal, T.A., et al., Effect of exacerbation on quality of life in patients with
chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 1998. 157(5 Pt 1): p.
1418-22.
3. Man, W.D., et al., Community pulmonary rehabilitation after hospitalisation for acute
exacerbations of chronic obstructive pulmonary disease: randomised controlled study.
BMJ, 2004. 329(7476): p. 1209.
Description of Study:
Based on the results of our pilot study [1], we hypothesise that early pulmonary
rehabilitation (EPR) leads to long term improvements in exercise capacity, quality of life,
use & resulting costs of healthcare resources, peripheral muscle strength and daily activity
levels. The null hypothesis is that EPR does not lead to a significant difference in outcome
when compared to usual care (UC).
EXPERIMENTAL DESIGN AND METHODS: This is a prospective randomised controlled clinical trial
of EPR vs. usual care.By using a control group, statistically significant differences in
outcome can be attributed to EPR. No treatment considered to be part of routine care is being
withheld from the UC group.
Patients: Patients studied will be those with an acute exacerbation of COPD deemed
sufficiently unwell by the duty medical registrar to warrant hospital admission. Exclusion
criteria will include significant co-morbidity that could limit exercise training, and
attendance at a pulmonary rehabilitation programme in the preceding year. In-patient
treatment will include standard therapy (nebulised bronchodilators, oxygen, non-invasive
ventilation (if required), antibiotics and a 1-2 week course of oral prednisolone 30-40mg
daily). On hospital discharge, patients will be allocated either to the early pulmonary
rehabilitation (EPR) group (within 7 days of hospital discharge) or usual care (UC) i.e.
routine outpatient and primary-care follow-up.
PROTOCOL: In the 48 hours before planned hospital discharge, the following measurements will
be made in all patients:
1. Pulmonary function tests, including ear-lobe blood gases, spirometry, lung volumes, and
transfer factor.
2. Anthropometric data, including height, weight, body mass index, lean body mass (as
measured by bio-electrical impedance)
3. Field exercise capacity as measured by the incremental shuttle walk, a standard
externally paced, incremental, maximal,corridor-walking test [2].
4. Disease-specific and generic health status, as measured by the Chronic Respiratory
Diseases Questionnaire (CRDQ) [3],St George's Respiratory Questionnaire (SGRQ) [4].
Interviews will take place in the lung function department at King's College Hospital.
5. Cardiopulmonary exercise testing in a subset of voulnteers, with measurements of VO2,
and VCO2 and lactic acid.
6. Non-volitional and volitional quadriceps strength: twitch quadriceps tension following
supramaximal stimulation of femoral nerve and maximum isometric voluntary contraction.
This is a painless supramaximal method of assessing quadriceps strength and fatigue [5]
[6].
7. Endurance walking capacity (endurance shuttle walk)
8. Health resource usage (see later). The EuroQol (EQ-5D) instrument [7] will be used as
the main measure of health-related quality-of-life in the economic evaluation.
The measurements made at baseline will be repeated at 3 and 12 months. Of note, as this study
is a prospective longitudinal study, patients will be familiarised with the exercise tests in
the days before discharge to minimise learning effect. Verbal encouragement during exercise
testing will be standardised to avoid researcher effects. The assessor will be blinded to the
subject's intervention. However owing to the nature of the intervention, it will not be
possible to blind the subjects to their intervention.
RANDOMISATION: At discharge, patients will be allocated to either a hospital outpatient
exercise rehabilitation programme, or usual care. Due to the numbers to be studied,
allocation of treatments using the minimisation method will be used to ensure comparable
groups. The following factors will be taken into account:
1. Age (above and below 70)
2. Gender (male/female)
3. Hospital Discharge incremental shuttle walk distance (more or less than 100 metres).
4. Length of Hospital Admission (more or less than 7 days)
5. FEV1 more or less than 30% predicted
INTERVENTION: Patients allocated to the EPR group will attend a pulmonary rehabilitation
programme within 7 days of hospital discharge. This will consist of two sessions a week for 8
weeks, and will be supervised by a multi-disciplinary team consisting of physiotherapists,
occupational therapists, nurses and dieticians as well as the clinical research fellow funded
by the proposed grant. Each session consists of 60 minutes exercise, made up of aerobic
walking and cycling exercise plus lower and upper limb strength and endurance exercise, and 1
hour of discussion focusing on psychosocial and lifestyle issues, with a particular emphasis
on nutrition and domestic activity. The EPR group will be also be given an individualised
home exercise programme, encouraging daily exercise. The UC group will receive usual
outpatient and primary care follow-up.
HEALTH ECONOMICS: The EuroQol (EQ-5D) instrument will be used as the main measure of
health-related quality-of-life in the economic evaluation [9]. It has been developed by a
collaborative group of European researchers as a preference-based index, suitable for the
calculation of QALYs. The EQ-5D is one of two instruments currently recommended for use in
economic evaluations [8]. Information on patients' use of health services will be collected
by a review of hospital notes, patient recall and a home diary issued to all study
participants. The resources included will be: hospital admissions, inpatient days, ITU days,
outpatient consultations, A&E attendances, and primary care surgery and home visits.
SAMPLE SIZE: Our preliminary pilot study was powered to detect a 50-metre difference in
incremental shuttle walk at the 5% significance level with 90% power. Based on the health
resource usage data collected from this pilot study, to detect a 50% reduction in hospital
readmission rate at the 5% significance level with 80% power would require a minimum of 60
patients (30 in each group). We propose to study 80 patients in this study
References:
1. Man, W.D., et al., Community pulmonary rehabilitation after hospitalisation for acute
exacerbations of chronic obstructive pulmonary disease: randomised controlled study.
BMJ, 2004. 329(7476): p. 1209.
2. Singh, S.J., et al., Development of a shuttle walking test of disability in patients
with chronic airways obstruction. Thorax, 1992. 47(12): p. 1019-24.
3. Guyatt, G.H., et al., A measure of quality of life for clinical trials in chronic lung
disease. Thorax, 1987. 42(10): p. 773-8.
4. Jones, P.W., et al., A self-complete measure of health status for chronic airflow
limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis, 1992. 145(6):
p. 1321-7.
5. Man, W.D., et al., Non-volitional assessment of skeletal muscle strength in patients
with chronic obstructive pulmonary disease. Thorax, 2003. 58(8): p. 665-9.
6. Polkey, M.I., et al., Quadriceps strength and fatigue assessed by magnetic stimulation
of the femoral nerve in man. Muscle Nerve, 1996. 19(5): p. 549-55.
7. Brooks, R., EuroQol: the current state of play. Health Policy, 1996. 37(1): p. 53-72.
8. Brazier, J., M. Deverill, and C. Green, A review of the use of health status measures in
economic evaluation. J Health Serv Res Policy, 1999. 4(3): p. 174-84.
