Clinical trial NCT05749731: Pan-European Study on Geriatric Rehabilitation After COVID-19 Disease
Official title: Pan-European Study on Outcome and Service in Geriatric Rehabilitation in Times of COVID-19 Pandemic
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Leids Universiteits Fonds
name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2023-03-01
Enrollment: 723
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be recruited from geriatric rehabilitation settings in the participating European countries (Czech Republic, Germany, Ireland, Israel, Italy, Malta, the Netherlands, Russia, Spain, United Kingdom) and consists of patients rehabilitating after a COVID-19 infection in these countries. There were no selection criteria concerning health or demographic characteristics.

Brief summary: Older and more vulnerable persons are more likely to get very ill when infected with the coronavirus, and have the highest COVID-19 morbidity and mortality rate. The majority of patients that are admitted to the hospital are older (\>70 years), and some of them have been admitted to Intensive Care Units (ICU). In the case of rehabilitation of older patients post-COVID-19, we do not know what the course of recovery for these patients will be, and what treatment/approaches will deliver the best outcomes.

Persons that are recovering from a COVID-19 infection, and admitted on a geriatric ward for early rehabilitation, or geriatric rehabilitation ward or facility, can be included in the study. They will receive routine, usual care; participation in this study will not affect their rehabilitation care. Routine care data will be collected from their electronic patient files at admission to geriatric rehabilitation, and at discharge. This also includes some data about their premorbid status. In addition, study participants will be called six weeks and six months after discharge from rehabilitation and asked some questions about their recovery. There is no risk association with participation in this study. Data will be anonymously collected in an online database.

The primary aim of this study is to get insight into the course of recovery in (geriatric) rehabilitation patients affected by COVID-19 in Europe. Mainly, we are interested in functioning in activities of daily living (ADL-functioning) such as toileting, bathing, dressing, etc., and in quality of life. The second aim of this study is to get insight into the treatment modalities employed and the organization of geriatric rehabilitation that post-COVID patients in Europe receive. Therefore, we collect data on the types of care provided and the professionals involved. Moreover, we collect some patient characteristics such as year of birth, gender, date of admission and date of discharge; and data about complications such as delirium, pain, post-traumatic stress syndrome, hospital readmissions, and mortality. Our hypothesis is that most patients will show recovery during geriatric rehabilitation and in the six months after. However, we expect that the amount and/or speed of recovery will vary between patients.

Detailed description: INTRODUCTION AND RATIONALE The COVID-19 pandemic has hit the world hard, and older and vulnerable persons are more likely to get very ill when infected, and have the highest morbidity and mortality. The majority of patients that are admitted to the hospital are older (\>70 years), and some of them have been, or are being, admitted to Intensive Care Units. Many patients stay on the ICU/hospital for weeks. To get back to the highest state of functional independence, these patients will need specialised care and treatment, therefore geriatric rehabilitation will be very likely required.

Geriatric Rehabilitation (GR) is defined as a multidimensional approach of diagnostic and therapeutic interventions, the purpose of which is to optimise functional capacity, promote activity and preserve functional reserve and social participation "in older people with disabling impairments." The goal of geriatric rehabilitation has been defined as "to assist \[older people\] to manage personal activities of daily living without the assistance of another person. If this is not possible, the goal is to minimize the need for external assistance through the use of adaptive techniques and equipment." Thereby focussing on the amelioration of dependency in activities of daily living. However, we are still in the dark about the amount of functional recovery of geriatric post-COVID-19 patients. We do know from the first lessons from Italy, that the rehabilitation process is difficult, and the course is capricious.

Before being able to assure the best outcomes for older post-COVID geriatric rehabilitation patients, we first have to be informed about what the clinical characteristics are, what treatment is provided, and what outcomes geriatric post-COVID-19 patients have in geriatric rehabilitation. Therefore, members of the Special Interest Group Geriatric Rehabilitation of the European Geriatric Medical Society (EuGMS) decided to conduct this multi-center observational cohort study into usual care data on the course of functional and clinical outcomes in post-COVID-19 geriatric rehabilitation patients in several European countries.

OBJECTIVES The primary objective of this study to get insight into the course of functional and medical recovery in (geriatric) rehabilitation patients affected by COVID-19 in Europe. The secondary objective is to get insight into the treatment modalities employed and the organisation of geriatric rehabilitation that post-COVID patients in Europe receive.

The study was conducted according to the principles of the Declaration of Helsinki (2013 version) and in accordance with the General Data Protection Regulation (GDPR) and in full conformity to any applicable state or local regulations in the participating countries.

RECRUITMENT In principle, patients admitted for geriatric rehabilitation due to COVID-19 morbidity will be informed by letter and asked if they have objections that their regular care data will be anonymously used for research purposes to improve practice in geriatric rehabilitation. If they do, the data will not be used (opt-out procedure). In some countries this will be conducted under the guidelines for service evaluation and audit, as it uses routine data, held entirely by the clinical care team. Where this is not possible because of local legislation or guidelines, informed consent will be obtained (opt-in procedure). During one-year (October 2020 - November 2021), patients were enrolled in the study.

Participants will receive standard rehabilitation treatment according to the discretion of clinical teams, which will likely be adapted to the specific needs of post-COVID-19 patients. This treatment includes physical therapy, occupational therapy, and medical treatment by an advanced nursing practitioner, geriatrician or medical specialist. This study will not influence any therapy provided or decisions about the medical treatment or treatment programs already used in the participating geriatric rehabilitation setting.

This study is observational and it is not anticipated that the observations will influence therapy or treatment, particularly since such indices, questionnaires and measurements are a regular part of the rehabilitation program.

STUDY MANAGEMENT For each participating geriatric rehabilitation facility in Europe one instructed local care professional will complete an online CASTOR database in which anonymous data from the clinical records of the included patients will be collected at admission, discharge and 6 weeks and 6 months follow-up. For countries with multiple participating sites, a country coordinator was appointed. Most country coordinators were the members of the Special Interest Group Geriatric Rehabilitation of the EuGMS.

DATA COLLECTION Variables collected

* Demographic factors: In all participants, selected demographic factors such as year of birth/age, gender, and residency premorbid will be documented.
* Information from hospital / general practitioner: hospital length of stay (days), ICU length of stay (days), complications during hospital stay or at home (Thromboembolism, Delirium, Pressure Ulcer), and COVID-19 diagnosis confirmed (PCR, Serology, clinically)
* At admission in geriatric rehabilitation: In all participants, only already routinely collected data will be documented. Such as ADL (Barthel index), quality of life (EQ-5D-5L), frailty (Clinical Frailty Scale), body mass index (BMI), nutritional status (MNA/NRS/MUST/SNAQ65/..), comorbidity (wFCI (0-36 pts)), cognition (MMSE/Demtect/ MOCA)) , delirium (DOS/SQiD), mood/anxiety (/GDS/HADS), pressure ulcer (yes/no), fatigue (VAS-scale), dyspnoea (VAS-scale), pain (NRS-P), mobility/balance (Timed Up and Go), muscle strength (MRC biceps /quadriceps), and speech/swallowing problems (yes/no)
* At discharge from geriatric rehabilitation: At discharge information about: hospital readmissions, length of stay in GR, discharge destination, ADL, frailty, BMI, nutrition, cognition, mood/anxiety, fatigue, dyspnoea, pain, mobility/balance, muscle strength, quality of life and complications during GR stay (Thromboembolism, Delirium, Pressure Ulcer) will be documented. At discharge we will additionally collect information about which professionals have been involved during geriatric rehabilitation an which treatment interventions have been applied.
* Follow-up after discharge: At 6 weeks and 6 months follow-up, and if desirable at flexible time points following regular care in the participating countries, we will document: ADL, Quality of life, post-traumatic stress syndrome.
* Qualitative data about countries' GR care services and triage systems: country coordinators in the study filled in a questionnaire about in what facility types GR for post-COVID-19 patients is provided (e.g. nursing homes, skilled nursing facility, acute care hospital ward, or on outpatient basis), which person refers the post-COVID-19 patients to GR (e.g. physician in the hospital, or GP), at which moment the referral takes place, which patient characteristics the referral is based on (e.g. standardized age cut-offs, frailty, multimorbidity, functional status, or psychosocial needs), which formal assessment is used for GR referral decisions, additional selection criteria by health insurance/policies, and criteria that need to be met by post-COVID patients for discharge from GR.

Data checks Data checks were performed during data collection to prepare for the steering board meetings that were held every two to three months with the country coordinators. In order to stimulate the achievement of the sample size, numbers of patients included were discussed during these meeting. Also structural missing or other remarkable things in the data were discussed during these meetings. Local care professionals were made aware of other missings or outliers in the data via email and asked to check and if possible complete or correct these data.

Sample Size calculation The primary outcomes are ADL functioning (Barthel index or derived from the USER or FIM) and quality of life (EQ-5D-5L). We performed a power calculation for a paired sample t-test on the primary outcome ADL-functioning (Barthel index). We assume a minimal clinically important difference of 2 points on the Barthel index as relevant, this is the mean difference between Barthel score at admission and Barthel score at discharge. The study would require a sample size of 52 (number of pairs) to achieve a power of 80% and a level of significance of 5% (two sided), for detecting a mean of the differences of 2 between pairs, assuming the standard deviation of the differences to be 5. We wanted to include a minimum of 52 patients per country which was agreed by the special interest group SIG EuGMS as being appropriate to generate the data we require. We aimed for a minimum of 250 participants in total.

STATSISTICAL ANALYSIS Different techniques will be used to analyze the data: Descriptive statistics will be used to give an overview of characteristics of the participants in the participating countries for all primary and secondary outcomes.

* For cross-country comparisons, we will perform a paired sample student t-test will be used to test the difference between ADL functioning at admission and follow-up per participating country, multilevel models will be built to model the recovery (in various outcome measures) of patients over time per country, supplemented with qualitative data about the countries' GR care services and triage systems.
* The course of recovery of post-COVID-19 patients over time (in various outcome measures) will be modelled with multilevel unconditional growth models. These multilevel models take into account that measurements are nested in patients and that patients are nested in countries. In doing so, the model with the best fitting shape (e.g. linear or quadratic) to our data will reveal the amount and speed of recovery.
* The impact of frailty on this course of recovery will be modelled, by adding the variable for frailty measured by the clinical frailty scale (CFS) to the models for the course of recovery.
* The impact of experiencing delirium during or prior to GR on this course of recovery will be modelled, by adding the variable delirium (yes/no) to the models for the course of recovery.
* (Potential) confounders of the impact of frailty on course of recovery and of the impact of delirium on the course of recovery such as age, sex, frailty status, delirium, and hospital stay, will be added to these
* By using descriptive statistics it will be described which post-COVID-19 GR patients receive which therapies/interventions during GR, and/or which professionals are involved in their GR trajectory.

No imputation will be used for missing data; complete case analysis will be performed, under the assumption that the data is missing at random.

The level of significance will be set at p \< 0.05.

Eligibility criteria: Inclusion Criteria:

* Recovering from a COVID-19 infection (confirmed with PCR, Serology, or clinically).
* Indication for geriatric rehabilitation

Exclusion Criteria:

* Presence of severe cognitive impairment, which leads to insufficient decisional capacities to participate in the study.
* Subjects who have opted for not using their anonymous data for research purposes

Primary outcomes:
measure: change in Activities of Daily Living (ADL)-functioning
timeFrame: Change in ADL-functioning from two weeks before admission to geriatric rehabilitation, until approximately 6 months after discharge from geriatric rehabilitation
Secondary outcomes:
measure: change in Quality of Life (EQ-5D-5L)
timeFrame: Change in quality of life from admission to geriatric rehabilitation until approximately 6 months after discharge from geriatric rehabilitation
Other outcomes:
measure: length of stay in geriatric rehabilitation
timeFrame: Date of discharge from geriatric rehabilitation minus data of admission to geriatric rehabilitation
measure: discharge destination
timeFrame: discharge destination is collected at discharge from geriatric rehabilitation (T2).
measure: mortality
timeFrame: date of death can be entered during geriatric rehabilitation (T2), at 6 weeks follow-up (T3), and at 6 months follow-up (T4).
measure: complications during rehabilitation
timeFrame: complications that occured between admission and discharge from geriatric rehabilitation.
measure: post traumatic stress disorder (PTSD)
timeFrame: PTSS is collected collected at 6 weeks follow-up (T3), and at 6 months follow-up (T4).
Locations:
city: Nové Město
country: Czechia
facility: Vseobecna fakultní nemocnice
city: Heidelberg
country: Germany
facility: Agaplesion Bethanien Hospital
city: Karlsruhe
country: Germany
facility: Geriatrisches Zentrum Karlsruhe
city: Mannheim
country: Germany
facility: Geriatrische Rehabilitationsklinik Diakonissenkrankenhaus Mannheim
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Limerick
country: Ireland
facility: University of Limerick Hospital Group (ULHG)
city: Haifa
country: Israel
facility: Fliman geriatric rehabilitation center
city: Milan
country: Italy
facility: IRCCS Istituti Clinici Maugeri
city: Valletta
country: Malta
facility: Karin Grech Hospital
city: Almelo
country: Netherlands
facility: TriviumMeulenbeltZorg
city: Almere
country: Netherlands
facility: Vivium Flevoburen (Zorggroep Almere)
city: Assen
country: Netherlands
facility: Icare - De Boshof
city: Beneden-Leeuwen
country: Netherlands
facility: Zorggroep Maas en Waal
city: Culemborg
country: Netherlands
facility: De Betuwe, Zorgcentrum Beatrix
city: De Steeg
country: Netherlands
facility: Attent
city: Delft
country: Netherlands
facility: Pieter van Foreest
city: Den Bosch
country: Netherlands
facility: Van Neynsel
city: Den Haag
country: Netherlands
facility: Florence
city: Eindhoven
country: Netherlands
facility: Archipel Zorggroep
city: Haarlem
country: Netherlands
facility: Kennemerhart Schoterhof
city: Harderwijk
country: Netherlands
facility: Reactiveringscentrum Klimop
city: Heerenveen
country: Netherlands
facility: Meriant (Alliade)
city: Hengelo
country: Netherlands
facility: TriviumMeulenbeltZorg
city: Middelburg
country: Netherlands
facility: SVRZ 't Gasthuis
city: Nieuwegein
country: Netherlands
facility: Zorgspectrum Nieuwegein
city: Rotterdam
country: Netherlands
facility: Laurens Intermezzo Zuid
city: Schiedam
country: Netherlands
facility: Argos Zorggroep
city: Sneek
country: Netherlands
facility: Patyna
city: Spijkenisse
country: Netherlands
facility: Careyn
city: Terborg
country: Netherlands
facility: Azora
city: Tilburg
country: Netherlands
facility: de Wever
city: Zevenaar
country: Netherlands
facility: Liemerije
city: Zutphen
country: Netherlands
facility: Sensire
city: Moscow
country: Russian Federation
facility: Moscow Rehabilitation center
city: Moscow
country: Russian Federation
facility: Russian Clinical and Research Center of Gerontology
city: Barcelona
country: Spain
facility: Consorci Sanitari Alt'Pènedes i Garraf
city: Barcelona
country: Spain
facility: Hospital de Barcelona
city: Barcelona
country: Spain
facility: Parc de Salut Mar
city: Barcelona
country: Spain
facility: Parc Sanitari Pere Virgili
city: Madrid
country: Spain
facility: Hospital Guadarrama
city: Madrid
country: Spain
facility: Hospital La Cruz Roja
city: Palma De Mallorca
country: Spain
facility: Hospital San Joan de Deu Mallorca
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus
city: Chesterfield
country: United Kingdom
facility: Derbyshire Community Health Services
city: Derby
country: United Kingdom
facility: University Hospitals of Derby and Burton
city: Frimley
country: United Kingdom
facility: Frimley NHS Trust
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
city: Huddersfield
country: United Kingdom
facility: Calderdale & Huddersfield
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield teaching Hospitals
Study officials:
affiliation: Department of Public Health and Primary Care, Leiden University Medical Cente
name: Monique AA Caljouw, Dr.
role: STUDY_CHAIR
affiliation: Department of Public Health and Primary Care, Leiden University Medical Cente
name: Wilco P Achterberg, Prof.
role: PRINCIPAL_INVESTIGATOR
References: