Clinical trial NCT04456036: Rehabilitation Needs and Functional Recovery in Covid-19 Acute and Post-acute Care
Official title: Rehabilitation Needs and Functional Recovery in Covid-19 Acute and Post-acute Care: Study of Functional Evolution, Predictors of Activities and Participation Recovery After Severe Covid-19 and Rehabilitation Role
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Keywords: COVID-19
Rehabilitation
Recovery of Function
Activities of Daily Living
Prognosis
Quality of Life
Continuity of Patient Care
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
Collaborators: name: Maria Gabriella Ceravolo
name: Michela Coccia
name: Lauredana Ercolani
name: Elisa Andrenelli
name: Lucia Pepa
name: Rossella Cima
name: Michela Aringolo
First posted: 2020-07-02
Enrollment: 100
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: Adults, male and female, admitted to the University Hospital "Ospedali Riuniti of Ancona" (UH-ORA) from March 1st, 2020 for the management of acute COVID-19 infection, able to provide written or oral informed consent. The only exclusion criterion will be the lack of information concerning clinical data regarding the management in the acute ward.

Brief summary: The purpose of the study is to apply a prospective observational design to describe the emerging functional impairments of subjects affected by COVID-19 in the acute phase and monitor their course and impact on activities and participation up to 12 months of onset. The ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19 survivors in each phase and foresee health needs in the medium and long term. The secondary objective of the study is to find predictors of functional recovery, among pre-existing and emerging individual and contextual factors, with a special focus on the latency of rehabilitation start after hospital admission.

Detailed description: The disease caused by SARS-CoV-2 infection, COronaVIrus Disease-19 (COVID-19), was first reported on December 31, 2019. About 20% patients, mostly elderly people, suffered from a severe form of acute respiratory failure. COVID-19 is a new clinical entity, therefore its understanding is largely incomplete, in particular as regards medium and long term consequences both in the clinical and functional domain. An early integration of rehabilitation care since the acute phase is often required to cope with the functional sequelae of the severe respiratory syndromes, as well of cardiac and neurological complications. However, indications, approaches, timing, amount and settings are mainly unknown due to the lack of epidemiological data regarding the impact of COVID-19 in terms of body function impairment and activity limitations in the short term and participation restrictions in the medium and long-term.

The purpose of the study is to apply a prospective observational design to describe the emerging functional impairments of subjects affected by COVID-19 in the acute phase and monitor their course and impact on activities and participation up to 12 months of onset. The ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19 survivors in each phase and foresee health needs in the medium and long term. The secondary objective of the study is to find predictors of functional recovery, among pre-existing and emerging individual and contextual factors, with a special focus on the latency of rehabilitation start after hospital admission.

The study protocol complements measures of functioning with the indicators used in the registration form for clinical characterization cases disseminated by the World Health Organization: in doing so, the authors aim to support the global project of providing Member States with a standardized approach to collect clinical data.

Study objectives Primary Objective: To describe the emerging functional impairments in patients hospitalized for SARS-COV-2 infection (COVID-19), and monitor their course and impact on activities and participation up to 12 months of onset Secondary Objective: To search for predictive factors of recovery, among the pre-existing and emerging individual and context-related ones. Particular attention will be paid to the presence and latency of rehabilitation delivery after hospital admission, describing the functional evolution of subjects who received rehabilitation since the acute phase, compared to those who did not.

MATERIALS AND METHODS. Study Design. Prospective observational study with 12-month follow-up. Total study duration: 18 months Population. Adults, male and female, admitted to the University Hospital "Ospedali Riuniti of Ancona" (UH-ORA) from March 1st, 2020 for the management of acute COVID-19 infection, able to provide written or oral informed consent. The only exclusion criterion will be the lack of information concerning clinical data regarding the management in the acute ward.

Data collection: A paper CRF and an eCRF will be implemented to record patients' data

* Clinical, laboratory and instrumental data collected in the acute phase will be retrieved, retrospectively, from patients' clinical records.
* Data concerning function impairments, activity limitations and participation restrictions will be collected through direct assessment carried out by the rehabilitation team at the enrollment, on the first referral of the patient for counseling (T0) and at hospital discharge (Td) (for those who will receive rehabilitation in the acute ward), as well as at 3 , 6 and 12 months of COVID-19 diagnosis (T3, T6, T12). Patient reported outcomes will be assessed through questionnaires and interviews, also delivered by telephone or video-consultation.

The primary endpoint is the change in the overall health status observed at enrolment (T0), compared to the pre-COVID-19 condition, and its evolution at 3, 6 and 12 months. To this aim, we will assess:

* independence in activities of daily living (ADLs), by the modified Rankin scale. The modified Rankin scale is a rapid and validated measure of global independence in ADL with a score ranging from 0 (no disability) to 5 (bedridden). To assess changes, the pre-COVID mod. Rankin scale score, retrospectively ascertained, will be compared to the scores prospectively collected at enrolment and at 3, 6 and 12 months
* walking performance, by the Walking Handicap scale (WHS). The Walking Handicap scale is a quick and validated measure of walking performance, with a score ranging from 1 (Physiological walker: Walks for exercise only either at home or in parallel bars during physical therapy) to 6 (Community walker: Independent in all home and community activities. Can accept crowds and uneven terrain. Demonstrates complete independence in shopping centers). To assess changes, the pre-COVID WHS score, retrospectively ascertained, will be compared to the scores prospectively collected at 3, 6 and 12 months
* health-related quality of life perception, by the 36-Item Short Form Survey (SF-36). SF-36 is a widespread validated scale assessing patient-reported changes in health-related well-being perception over the last 4 weeks. SF-36 scores will be collected at 3, 6 and 12 months.

The secondary endpoint is the identification of the predictors of functional recovery at 3, 6 and 12 months, among the pre-existing and emerging individual and context-related factors.

The following explanatory variables will be considered:

* Pre-existing individual factors: age, gender, blood type, nutritional status, comorbidity (Modified Cumulative Illness Rating Scale - CIRS), life habits and pre-existing disability (modified Rankin Scale and Walking Handicap scale in pre-COVID phase)
* Emerging individual factors: severity of COVID-19 on admission to the acute ward, severity of pneumonia during hospitalization (according to Li et al 2020), blood chemistry (e.g. levels of interleukine, albumin, creatinine, CRP), pulmonary thromboembolism, neurologic complications, swallow disorders in the acute phase; severity of body function impairment and activity limitation on enrolment (as measured by the Trunk control test-TCT, Standing Balance-SB, Functional Ambulation Category-FAC, modified Barthel index- mBI, Montreal Cognitive Assessment-MoCA)
* Emerging context-related factors: drug treatment in the acute phase (e.g. ACE inhibitors, Angiotensin II receptor blockers, Nonsteroidal anti-inflammatories, Antivirals, heparin), procedures adopted in the ICU (prone positioning, tracheostomy, support for ventilation, ECMO, Renal replacement therapy or dialysis, Inotropes/vasopressors), rehabilitation delivery in the acute ward and latency from hospital admission to rehabilitation start.

Clinical-functional evaluations will be carried out at the following time-points:

T0 = on enrolment Td = discharge from the acute ward (only for subjects who are enrolled during their stay in the acute ward) T3, T6, T12 = three, six and 12 months after hospital admission due to COVID-19 infection.

After discharge from hospital, the assessments will be carried out in the outpatient laboratory; in case of mobility restrictions, questionnaires will be delivered and interviews will be conducted by telephone or by video consulting.

Sample size and data analysis. Given the nature of the study, a formal calculation of the sample size was not made. The enrolment of at least 100 subjects is estimated based on COVID-19 incidence in the catchment population of the UH-ORA.

A descriptive analysis will be conducted on the collected variables using point estimates and variability measures for quantitative variables or absolute and relative frequencies for category variables.

A multivariate model will be constructed to extrapolate predictors of poor recovery at 12 months (i.e. Delta T12-T0 on modified Rankin score : \>1), by adjusting for potential confounders. After checking for the normal distribution of quantitative measures, the analysis of variance (ANOVA) for repeated measures will be applied to analyze the distribution of functional outcome measures, at 3, 6 and 12 months, among those who received rehabilitation in the acute phase, respect to those who did not.

Eligibility criteria: Inclusion Criteria:

* age \>= 18 years,
* any gender,
* COVID-19 diagnosis: positive oro-pharyngeal swab for SARS-COV-2
* admitted to the University Hospital "Ospedali Riuniti of Ancona" (UH-ORA) from March 1st, 2020 for the management of acute COVID-19,
* able to provide written or oral informed consent.

Exclusion Criteria:

* the lack of information concerning clinical data regarding the management in the acute ward.

Primary outcomes:
measure: Change from pre-COVID-19 condition in ADL independence on the mod. Rankin scale score at the enrolment (T0) assessment, at 3, 6 and 12 months
timeFrame: Pre-COVID status, at enrolment and at 3, 6 12-month follow-up
measure: Change from pre-COVID-19 condition in walking performance on the Walking Handicap scale (WHS) at 3, 6 and 12 months
timeFrame: Pre-COVID status , and 3, 6 12-month follow-up
measure: Patient-reported health-related well-being perception on the 36-Item Short Form Survey - SF-36 at 3, 6 12 months follow-up
timeFrame: 3, 6 and 12-month follow-up
Secondary outcomes:
measure: Change in global ADL disability on modified Barthel Index (mBI), from the enrolment (T0), at 3, 6 12 months follow-up
timeFrame: the enrolment (T0) assesssment and 3, 6 and 12-month follow-up
measure: Change in walking capacity on Functional Ambulation Category (FAC), from the enrolment (T0) assessment, at 3, 6 12 months follow-up
timeFrame: Pre-COVID status, the enrollment (T0) assessment and 3, 6 12-month follow-up
measure: Change in cognitive abilities on the Montreal Cognitive Assessment (MoCA) from the enrollment (T0) assessment, at 3, 6 12 months follow-up
timeFrame: the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up
measure: Change in patient-reported pain on Numerical Rating Scale from the enrollment (T0) assessment, at 3, 6 12 months follow-up
timeFrame: the enrollment (T0) and 3, 6 and 12-month assessment follow-up
measure: Change in swallow abilities on Dysphagia Outcome Severity Scale (DOSS) from the first functional assessment in acute care, at 3, 6 12 months follow-up
timeFrame: the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up
measure: Change in endurance on 6-Minutes Walking Test (6MWT) from the enrolment (T0) assessment, at 3, 6 12 months follow-up
timeFrame: the enrolment (T0) and 3, 6 and 12-month assessment follow-up
measure: Change in mood status on Beck Depression Inventory (BDI) from the enrolment (T0) assessment, at 3, 6 and 12 month follow-up
timeFrame: enrolment (T0) assessment and 3, 6 and 12-month assessment follow-up
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Neurorehabilitation Clinic, University Hospital Ospedali Riuniti di Ancona
Study officials:
affiliation: Dep. of Experimental and Clinical Medicine - University Politecnica delle Marche
name: Maria Gabriella Ceravolo, MD PhD
role: STUDY_DIRECTOR
References:
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