Chronic Obstructive Pulmonary Disease Clinical Trial
Official title:
Pilot Feasibility Study to Determine the Clinical Effectiveness of Neural Respiratory Drive (NRD) to Predict COPD Exacerbations at Home.
COPD is a common, serious disease and is a major burden on patients and the National Health
Service. Patients with COPD can develop worsening of their symptoms, known as an
exacerbation, which can be severe enough to warrant hospital admission. There are currently
no objective measurements available to patients and clinicians to predict exacerbation and
monitor recovery. Detection of exacerbation by both patients and physicians is known to
correlate poorly with onset of respiratory deterioration.
Measurement of neural respiratory drive (NRD), or drive to breathe, using respiratory muscle
electromyography (EMG) correlates with changes in patients' symptoms and physician defined
deterioration during hospital admissions.
This pilot study aims to identify whether daily measurement of NRD at home following
admission to hospital with exacerbation of COPD can detect an exacerbation within 30 days of
discharge (20% of patients are readmitted within this period). This technique could enable
early detection of deterioration at home, facilitating earlier treatment compared to current
practice, potentially avoiding hospital readmission.
30 patients admitted to St Thomas' Hospital because of an exacerbation of COPD aged 40-80,
with a body mass index <35kg/m2, who can follow English instructions and give informed
consent, who are discharged home will be recruited. If patients consent to participate, they
will have assessments as inpatients and for 30 days at home following discharge, or until
hospital readmission, whichever is sooner. Assessments include vital observations (heart
rate, blood pressure, respiratory rate and oxygen saturations), NRD, and a symptom
questionnaire. At the baseline assessment, age, height weight, a brief medical history,
results of tests already taken by the clinical team (blood tests and chest x-ray) and lung
function tests will be recorded. This study will take 12 months. Philips and its Affiliates
are providing the NRD measuring equipment.
Introduction
COPD is a common and serious disease, and is a major burden on patients and the National
Health Service. Current markers to detect and monitor exacerbations and response to treatment
are based on symptoms reported by patients, clinical assessment and Early Warning Scores,
which are a composite measurement of standard observations, including heart rate, blood
pressure, respiratory rate and oxygen saturations. However these scores have been validated
on general populations and there is concern regarding their application to COPD patients.
There is currently no objective biomarker to predict and monitor COPD exacerbations in
routine clinical use.
NRD is measured using parasternal intercostal EMG measurements. Daily NRD measurements during
hospital admission with exacerbation of COPD has been demonstrated to be a reproducible
non-invasive measurement which is acceptable to patients. Importantly, it can reliably detect
clinical deterioration and worsening in patient reported breathlessness more reliably than
current standard assessments.
This observational pilot feasibility study is designed to identify whether NRD can be
measured reliably at home following discharge from hospital with exacerbation of COPD, and
whether it can detect respiratory deterioration within 30 days. This technique thus has the
potential to allow early detection of deterioration at home, which can facilitate early
treatment in the community and potentially avoid hospital readmission, which would have a
profound impact on both patients and the NHS.
Study objectives
Primary: The primary objective of the study is to investigate whether home measurement of NRD
can detect an exacerbation of COPD (symptom based definition) within a 30-day post hospital
discharge period.
Secondary
Clinical:
- To validate NRD as an advanced physiological biomarker of clinical respiratory
deterioration and a re-exacerbation of COPD
- To analyse NRD trajectory as it relates to standardly subjective measurements of
respiratory symptoms e.g. COPD Assessment Test (CAT) and Modified Borg Scale (mBorg), or
symptoms as assessed by the EXACT-PRO questionnaire
- To determine positive and negative predictive value of NRD, and/or a combination of
clinical features, to detect clinical respiratory deterioration
- To assess correlation of change in NRD, physical activity and symptom resolution
Feasibility:
-To investigate quality of parasternal EMG measurements performed in the home environment
Technical:
-To use the data collected during the study to tune, refine, optimise the automated NRD
calculation algorithm
Study end-points Primary end-point: Change in NRD from baseline to day prior to an acute
exacerbation of COPD.
Secondary outcomes
- Change in NRD from peak exacerbation (hospital) to recovery baseline (home)
- Correlation of time to recovery as measured by NRD and EXACT-PRO
- Correlation of NRD to EXACT-PRO from hospital discharge to recovery
- Correlation of NRD to physical activity from hospital discharge to recovery
- Physician-assessed exacerbation within 30-day post-discharge
- Self-treated exacerbation within 30-day post-discharge
- All cause hospital readmission within 30-day post-discharge
- Mortality within 30-day post-discharge
- Recovery as defined by the EXACT-PRO within 30-day post-discharge
- Medication change within 30-day post-discharge
- Unplanned healthcare contacts
- Attendance of emergency department (without admission)
Methods
30 consecutive patients admitted to St Thomas' Hospital with a primary diagnosis of
exacerbation of COPD will be enrolled within 16 hours of admission who fulfil inclusion and
exclusion criteria (listed below). Baseline assessments will include recording of age,
height, weight, pack year smoking history, exacerbation frequency, pre-admission lung
function and breathlessness score, co-morbidities, regular medications, chest x-ray, venous
and arterial blood test results already taken by the medical team, symptom questionnaires
(CAT, mBorg and EXACT-PRO), vital observations (heart rate, blood pressure, respiratory rate,
oxygen saturation and use of supplementary oxygen), lung function and NRD. Participants will
receive inpatient assessments by an investigator to receive an update from the clinical team
and measure standard observations, NRD and complete the EXACT-PRO questionnaire. On the day
of discharge, participants' updated medical history and blood tests will be documented and
vital observations, symptom questionnaires (CAT, mBorg and EXACT-PRO), lung function and NRD
will be measured. Participants will be issued with a physical activity monitor which will be
worn for the remaining duration of the study. Participants will then receive home visits from
an investigator, who are experienced in the management of COPD, to measure NRD, complete the
EXACT-PRO symptom questionnaire and review participants' daily symptom diary. Lung function
and the CAT symptom questionnaire will be performed weekly at home. Participants will be
followed up for 30 days following hospital discharge or until they are readmitted to
hospital, whichever is sooner.
Study design: Observational cohort design
Inclusion criteria
- Age 40-80 years
- Patients hospitalised with a primary diagnosis of an acute exacerbation of COPD
- Body mass index (BMI) ≤ 35 kg/m2
- Cognitively and linguistically able to follow instructions given in English and provide
informed consent
- To be discharged to home following the hospitalisation
- Patient lives in the catchment area served by the Integrated Respiratory Team at Guy's
and St Thomas' NHS Foundation Trust in a home environment deemed safe by the
investigators to perform home assessments
Exclusion criteria
- Previous home PAP (CPAP or NIV) therapy use within the past year, or post-discharge
- Allergies to latex, metals or local anaesthetic agents
- Wound or inflamed skin at parasternal location (2nd intercostal space)
- History of skin allergies or sensitivity to cosmetics and lotions
- Psychological and social factors that would impair compliance with study protocol and
schedule
- Any major non-COPD chronic disease or condition, such as severe heart failure
(LVEF<30%), malignancy (active treatment and palliation), end stage renal
failure/dialysis, significant neuromuscular disease (eg. NMD, MD) determined by review
of medical history and / or patient reported medical history that may contribute
significantly to risk of readmission, as determined by PI
- Length of stay < 6 hours
- Planned travel away from home within the 30 day post discharge period
Consent:
Patient will be provided with a patient information sheet and have a minimum of one hour to
consider trial participation. A longer period for consideration of trial participation can be
provided if required by the patient, however baseline assessments must be made within 16
hours of hospital admission.
Risk and benefit:
Sticker placement for the EMG electrodes may require participants to shave their chest. The
adhesive stickers and the skin preparation gel may cause minor skin irritation. Participants
are required to perform sniff manoeuvres as part of NRD measurement which may feel
uncomfortable. Participants will be advised to breath normally should they feel light headed
or breathless.
There will be no direct benefit to individual participants. However the study aims to develop
a technique that can be used to predict and prevent hospital readmission following admission
with exacerbation of COPD, which will have benefits for the wider community of patients and
the NHS.
Confidentiality:
Participants' name, date of birth and other identifiable information will be collected during
the study phase. All stored data will be in line with the Caldicott principals, data
protection and REC guidelines.
Conflicts of interest:
There are no perceived conflicts of interest. Participants' supervising consultants will
remain responsible for clinical care and will not be involved in the collection or
interpretation of the research data, which will be performed by a dedicated research team.
Tissue and biological samples:
No tissue or biological samples will be obtained for the study protocol outside of routine
care.
Protocol amendments:
In September 2018, the following amendments were made to the protocol which were approved by
the London-Westminster Research Ethics Committee:
- Addition of the Modified Borg Score to daily assessments to measure subjective
breathlessness intensity
- Inclusion criterion six was amended so that participants must live in the catchment area
served by the Integrated Respiratory Team (not the "Lane Fox Respiratory Unit") at Guy's
and St Thomas' NHS Foundation Trust for clinical, safety and practical purposes.
- Collection of hospital admission, healthcare utilisation and mortality data following
study participation from electronic medical records
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