Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04649957 |
| Other study ID # |
COVID-19-UoD&RDH20/21 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2021 |
| Est. completion date |
December 21, 2023 |
Study information
| Verified date |
December 2023 |
| Source |
University of Derby |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Currently, there are few studies that have been established that consist of a variety of
established and coherent approaches that sought to profile the determinants of recovery, nor
used interrogative procedures to understand lasting physical impairment. In this context,
measurements obtained from an assessment of cardio-respiratory responses to physiological
stress could provide an important insight regarding the integrity of the pulmonary-vascular
interface and characterisation of any impairment or abnormal cardio-respiratory function [4].
Indeed, current approaches are being developed to support patients using previous knowledge
from other acute respiratory infections (e.g. Acute Respiratory Distress Syndrome; ARDS and
Middle Eastern Respiratory Syndrome; MERS), approaches that do not consider the novel
challenges presented by COVID-19. The knowledge obtained from the proposed research plan will
inform the development of COVID-19 specific rehabilitation and clinical management guidelines
which can be implemented globally to increase patient wellbeing, physical capacity, and
functional status which will be directly related national and international health and
wellbeing, economical and societal impacts.
Description:
3.1 Screening and Eligibility Assessment Study investigators will identify eligible
participants within 72 hours of expected discharge from hospital. Eligibility will be
determined using the criteria outlined which incorporates the Post-COVID-19 Functional Status
(PCFS) Scale, a tool which has been developed and endorsed by the European Respiratory
Society to measure functional status over time following COVID-19 infection. Patients graded
2, 3 or 4 on the PCFS will be eligible for participation. Eligible patients will be provided
with a detailed explanation of the study including the provision of written information
(PIS). Patients will be given time to consider participation in the research study before
being approached again by the research team.
If the patient expresses an interest in study participation the research team will invite
participants to a baseline data collection session that will be held at the University of
Derby in the days following discharge.
3.2 Assessments: Upon enrolment, admission clinical data and the results of investigations
undertaken as part of the participants' usual care, before study enrolment will be collected,
as outlined below. In the days following discharge (2 +/- 2 days) participants will complete
a baseline assessments and measurements, outlined below and in the schedule of procedures.
At days 14, 42, 70, 98 (+/- 2 days) participants will conduct a consultation via telephone
where all scales and questionnaires completed at baseline will be repeated (see the schedule
of procedures outlined below). The total duration of these consultations' will be 15 minutes
each time.
At Days 28, 56, 84, 112, 140 and 168 (+/- 2 days) participants will be attend a face to face
appointment at the University of Derby's Human Performance Unit where physiological,
biological, cognitive, and patient-reported outcome measures will be completed (see the
schedule of procedures outlined below).
Where face to face or telephone consultations fall over a weekend (Saturday or Sunday) these
will be arranged to occur on either the Friday before or Monday after, as convenient for the
participant, but not more than 2 days away from the original date. The total duration of
these research assessments will be 60 minutes per visit. All follow up appointments will be
confirmed one week before the scheduled date via telephone/e-mail consultation. Acting as a
reminder and to confirm the availability of the patient.
Schedule of Procedures
3.2.1 Baseline Clinical Data: Data collected will include demographics, the pre-admission
symptoms, pre-admission therapy, pre-admission exercise tolerance and performance status
(retrospective assessment by the patient and/or representative 6 weeks preceding admission)
level of educational attainment, past-medical history, time and route of admission, and
in-hospital routine physiological observations (including heart rate, blood pressure, oxygen
saturation, respiratory rate and temperature). To ensure consistent recording of data across
participants, we will collect the first set of physiological observations taken at / closest
to 08.00 am on the morning of discharge.
3.2.2 Routine Clinical Investigations: The results of clinical investigations routinely
performed during the participants' hospital admission, including those performed before study
enrolment, will be collected including; blood parameters on admission to hospital full blood
count (FBC), d-dimers, ferritin and Interleukin 6 (IL-6) Lactate dehydrogenase (LDH). If a
radiological investigation was performed, the first investigation following admission will be
recorded.
3.2.3 Post-COVID-19 Functional Status (PCFS) Scale The Post-COVID-19 Functional Status (PCFS)
Scale will be assessed upon discharge from the hospital and during each face to face visit to
monitor direct recovery and to assess functional sequelae. The PCFS will evaluate the
ultimate consequences of COVID-19 on functional status and supplement other instruments that
measure quality of life, tiredness, or dyspnoea in the acute phase. The PCFS covers the full
spectrum of functional outcomes and focuses on both limitations in usual duties/activities
and changes in lifestyle in six scale grades. Briefly grade 0 reflects the absence of any
functional limitation, and the death of a patient is recorded in grade D. Upward of grade 1,
symptoms, pain or anxiety are present to an increasing degree. This has no effect on
activities for patients in grade 1, whereas a lower intensity of the activities is required
for those in grade 2. Grade 3 accounts for inability to perform certain activities forcing
patients to structurally modify these. Finally, grade 4 is reserved for those patients with
severe functional limitations requiring assistance with activities of daily living (ADL).
3.2.3 Biomarkers: In-line with the outlined biomarkers in section 3.2.1, participants will
have a serum sample taken for the measurement of inflammatory and metabolic biomarkers,
including full blood count (to determine neutrophil leukocyte ratio (NLR) and the polymorph
lymphocyte ratio (PLR), C-reactive protein (CRP), ferritin, d-dimers, ferritin and
Interleukin 6 will be at discharge (Day 0). These samples are in addition to those collected
during routine clinical care. Blood will be aliquoted, frozen, and stored for batch testing
of biomarkers. These biomarkers have been selected because it has previously been
demonstrated to correlate with a persistent reduction in quality of life scores. Participants
will be asked to provide permission for the retention of these samples and consent for their
use in future COVID-19 research studies.
3.2.4 Quality of Life: The EQ-5D-5L is routinely used in the assessment of the quality of
life in respiratory research and is available in more than 130 languages (EQ-5D-5L, Appendix
XX). It comprises five dimensions (previously 3): mobility, self-care, usual activities,
pain/discomfort, and anxiety/depression. Each dimension has five levels: no problems, slight
problems, moderate problems, severe problems, and extreme problems.
3.2.5 Lung and Respiratory Muscle Function: Full lung function tests including FEV1 (forced
expiratory volume at one second), FVC (forced vital capacity), PEFR (peak expiratory flow
rate), flow-volume curves, MIP (maximal inspiratory pressure) and MEP (maximum expiratory
pressure) will be measured at the hospital visits conducted at Day 0, all subsequent follow
up appointments. These spirometry measurements will be conducted by a suitably qualified
individual, proficient in the use of the specific equipment and according to published
standards.
3.2.6 Symptom Profile: Symptom profile will be measured twice at the discharge assessment
(Day 0), to capture a) retrospective assessment by the patient of their symptom status 6
weeks before admission (essentially their baseline symptoms before acute illness or
admission), and b) their current symptom status at the point of discharge from hospital), and
once at each subsequent weekly follow-up contact (either hospital visit or telephone
consultation).
Fatigue is a common complaint in patients recovering from an acute respiratory infection and
is not adequately captured in general quality of life or specific recovery questionnaires.
Participants will complete 2 separate measures of fatigue at discharge (Day 0) and each
subsequent follow-up contact; (A) the Fatigue Assessment Scale (FAS), a self-reported
questionnaire validated to assess presence and severity of fatigue; and (B) MFI-20. A 20 item
self-reported questionnaire assessing fatigue across five aspects.
The Medical Research Council (MRC) Dyspnoea Scale (MRC) is a measure to grade the effect of
breathlessness on the person's daily activities. The MRC is simple to administer and is a
short 1-5 stage scale (1 item) and allows the person to state the extent to which their
breathlessness affects their mobility.
3.2.7 Cognition: The Montreal Cognitive Assessment (MoCA) will be conducted at discharge (Day
0) and again at Day 168. To reduce the impact of learning effect 2 distinct versions of the
MoCA will be used as recommended by the developers, one at point of discharge, and repeat
assessment at 168-day follow-up. To allow accurate interpretation, highest educational
level/attainment will be recorded during the data collection phase of the study (before
discharge).
3.2.8 Functional Status: Two different assessments of lower extremity functional capacity
will be conducted at each visit these are (A) the 6-minute walk test (6MWT) and (B) the timed
up and go test (TUG). The 6MWT is a standardised and widely used measure of functional status
in individuals with chronic disease such as chronic obstructive pulmonary disease, cystic
fibrosis, congestive cardiac failure, peripheral vascular disease, and elderly. It has been
previously used to assess response to interventions and predict morbidity and mortality.
Participants will be given a shortened practice attempt (1-2 minutes) at the beginning of
each of their assessment visits. This will not be recorded but will be performed to allow
familiarisation with the assessment and repeated at each visit for consistency.
The TUG is reliable and reproducible and has been validated as a predictor of frailty and
risk of falls in elderly adults. The TUG has several advantages over other measures, mainly
its reproducibility and shorter assessment time. Its use at predicting functional status
following pneumonia has not been assessed previously.
Participants will also be asked to self-report their return to functional activity and
employment at each contact with the research team (telephone consultations and follow-up
visits.) Each participant will be asked at each contact with the research team if they have
returned to perform their activities of daily living to the same level as 6 weeks before
admission, and if they have returned to their occupation (if employed.) The patient-reported
date of return to these activities will also be recorded.
3.2.10 Sleep Behaviour: Participants will complete the Pittsburgh Sleep Quality Index (PSQI).
The PSQI is a self-report measure to assess sleep quality over a 4 week in period, throughout
the intervention. The measure consists of 19 individual items, with a 0-3 interval scale and
creates 7 components that produce one global score. The PSQI is reliable and valid in the
assessment of sleep problems.
3.2.11 Patient Experiences of COVID-19 Recovery Patient experiences of their recovery will be
recorded via a free text weekly diary. Patients will be asked to provide free-text details
about their experience throughout the week and to highlight any perceived changes in their
symptom profile, recovery, and quality of life.
3.4 Description of Statistical Method: Statistical analysis will be supervised by Dr Emma
Sharpe at the University of Derby and conducted using SPSS version 26. This study is a
prospective observational cohort study, designed to identify suitable tools and measures
across different domains for assessing patient recovery from COVID-19. Descriptive statistics
will be calculated for all outcomes of interest. These will be presented as proportions and
means with standard deviations or medians with interquartile ranges, depending on the
distribution of data. Data will be collected at baseline and via face to face visits
occurring every 28 days (days 28, 56, 84 and 112) which will be interspersed with telephone
consultations, again occurring each 28 days (days 42, 70 and 98). Categorical data will be
assessed using Chi-squared tests, whilst continuous outcome data will be analysed using
Independent samples t-test or Mann-Whitney U test depending on the distribution. All
qualitative components will be grouped collated upon study completion and analysed using
Interpretative Phenomenological Analysis (IPA) in accordance with the methods proposed by
Smith, Flowers and Larkin (2009).
