Long-term Follow up in Survivors of Critical Illness

• ClinicalTrials.gov Identifier: NCT04608994
• Recruitment Status: Unknown
• First Posted: October 30, 2020
• Last Update Posted: October 30, 2020
• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Collaborator: Università degli Studi di Brescia
• Information provided by (Responsible Party): Piva Simone, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Tracking Information

• First Submitted Date: October 3, 2020
• First Posted Date: October 30, 2020
• Last Update Posted Date: October 30, 2020
• Actual Study Start Date: June 1, 2020
• Estimated Primary Completion Date: June 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2020)

• Medical Research Council (MRC) sum score [ Time Frame: 3 months ]
  Medical Research Council (MRC)-sum score evaluates global muscle strength, and it has been proposed in PICS syndrome post-COVID-19. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using the MRC-sumscore. The summation of scores gives MRC-sumscore, ranging from 0 to 60. This score reliably identifies significant weakness (< 48) and even better in severe weakness (<36).
• Medical Research Council (MRC) sum score [ Time Frame: 6 months ]
  Medical Research Council (MRC)-sum score evaluates global muscle strength, and it has been proposed in PICS syndrome post-COVID-19. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using the MRC-sumscore. The summation of scores gives MRC-sumscore, ranging from 0 to 60. This score reliably identifies significant weakness (< 48) and even better in severe weakness (<36).
• Medical Research Council (MRC) sum score [ Time Frame: 12 months ]
  Medical Research Council (MRC)-sum score evaluates global muscle strength, and it has been proposed in PICS syndrome post-COVID-19. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using the MRC-sumscore. The summation of scores gives MRC-sumscore, ranging from 0 to 60. This score reliably identifies significant weakness (< 48) and even better in severe weakness (<36).
• Dominand Handgrip Test [ Time Frame: 3 months ]
  Dynamometry will be considered normal if >11Kg in Male and 7.5 kg in Female. Moreover, the researcher will standardized the result as percentage of the predicted normal value (PNV) as follow: <20% PNV; 20%<=PNV< 40%; 40%<=PNV< 60%; 60%<= PNV< 80%, and >=80 PNV. [DOI: 10.1016/j.clnu.2008.04.004]
• Dominand Handgrip Test [ Time Frame: 6 months ]
  Dynamometry will be considered normal if >11Kg in Male and 7.5 kg in Female. Moreover, the researcher will standardized the result as percentage of the predicted normal value (PNV) as follow: <20% PNV; 20%<=PNV< 40%; 40%<=PNV< 60%; 60%<= PNV< 80%, and >=80 PNV. [DOI: 10.1016/j.clnu.2008.04.004]
• Dominand Handgrip Test [ Time Frame: 12 months ]
  Dynamometry will be considered normal if >11Kg in Male and 7.5 kg in Female. Moreover, the researcher will standardized the result as percentage of the predicted normal value (PNV) as follow: <20% PNV; 20%<=PNV< 40%; 40%<=PNV< 60%; 60%<= PNV< 80%, and >=80 PNV. [DOI: 10.1016/j.clnu.2008.04.004]
• Six Minutes Walking Test [ Time Frame: 3 months ]
  Six-minute walking test will be performed in accordance with the America Thoracic Society recommendations and it will be adjusted for age, sex, height, and body weight
• Six Minutes Walking Test [ Time Frame: 6 months ]
  Six-minute walking test will be performed in accordance with the America Thoracic Society recommendations and it will be adjusted for age, sex, height, and body weight
• SIX Minutes Walking Test [ Time Frame: 12 months ]
  Six-minute walking test will be performed in accordance with the America Thoracic Society recommendations and it will be adjusted for age, sex, height, and body weight
• Fatigue Severity Scale (FSS) [ Time Frame: 3 months ]
  The Fatigue severity score is a nine-item unidimensional questionnaire that measures the severity of fatigue symptoms on a seven-point ordinal scale (maximum score of seven). An FSS ≥36 will be considered as an indicator of fatigue.
• Fatigue Severity Scale (FSS) [ Time Frame: 6 months ]
  The Fatigue severity score is a nine-item unidimensional questionnaire that measures the severity of fatigue symptoms on a seven-point ordinal scale (maximum score of seven). An FSS ≥36 will be considered as an indicator of fatigue.
• Fatigue Severity Scale (FSS) [ Time Frame: 12 months ]
  The Fatigue severity score is a nine-item unidimensional questionnaire that measures the severity of fatigue symptoms on a seven-point ordinal scale (maximum score of seven). An FSS ≥36 will be considered as an indicator of fatigue.
• Elettromyography [ Time Frame: 3 months ]
  Simplified peroneal nerve test (PENT)wiil be used to diagnose a critical illness polyneuropathy and myopathy; a value <5.26 mV present in both legs was considered as abnormal.
• Elettromyography [ Time Frame: 6 months ]
  Simplified peroneal nerve test (PENT)wiil be used to diagnose a critical illness polyneuropathy and myopathy; a value <5.26 mV present in both legs was considered as abnormal.
• Elettromyography [ Time Frame: 12 months ]
  Simplified peroneal nerve test (PENT)wiil be used to diagnose a critical illness polyneuropathy and myopathy; a value <5.26 mV present in both legs was considered as abnormal.
• Montreal Cognitive Assessment Test (MoCA) [ Time Frame: 3 months ]
  Montreal Cognitive Assessment (MoCA) is divided into several cognitive domains with variable scoring among them, adding up to a maximum total of 30 points if all responses are correct. The scale is divided into Visuospatial and executive functioning (5 points), animal naming (3 points), attention (6 points), language (3 points), abstraction (2 points), delayed recall (short-term memory, 5 points), and orientation (6 points). To correct for educational effects found in the original study, one point is added if the subject has less than 12 years of education. The suggested cutoff score for normalcy in the MoCA is 26/30. When patients scored less than 26, we used the following classification: 18-25 = mild cognitive impairment, 10-17= moderate cognitive impairment, and less than 10= severe cognitive impairment
• Montreal Cognitive Assessment Test (MoCA) [ Time Frame: 6 months ]
  Montreal Cognitive Assessment (MoCA) is divided into several cognitive domains with variable scoring among them, adding up to a maximum total of 30 points if all responses are correct. The scale is divided into Visuospatial and executive functioning (5 points), animal naming (3 points), attention (6 points), language (3 points), abstraction (2 points), delayed recall (short-term memory, 5 points), and orientation (6 points). To correct for educational effects found in the original study, one point is added if the subject has less than 12 years of education. The suggested cutoff score for normalcy in the MoCA is 26/30. When patients scored less than 26, we used the following classification: 18-25 = mild cognitive impairment, 10-17= moderate cognitive impairment, and less than 10= severe cognitive impairment
• Montreal Cognitive Assessment Test (MoCA) [ Time Frame: 12 months ]
  Montreal Cognitive Assessment (MoCA) is divided into several cognitive domains with variable scoring among them, adding up to a maximum total of 30 points if all responses are correct. The scale is divided into Visuospatial and executive functioning (5 points), animal naming (3 points), attention (6 points), language (3 points), abstraction (2 points), delayed recall (short-term memory, 5 points), and orientation (6 points). To correct for educational effects found in the original study, one point is added if the subject has less than 12 years of education. The suggested cutoff score for normalcy in the MoCA is 26/30. When patients scored less than 26, we used the following classification: 18-25 = mild cognitive impairment, 10-17= moderate cognitive impairment, and less than 10= severe cognitive impairment
• Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 months ]
  Hospital Anxiety and Depression Scale (HADS) was classified as follow: HADS for depression: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case) and HADS Anxiety: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case).
• Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 6 months ]
  Hospital Anxiety and Depression Scale (HADS) was classified as follow: HADS for depression: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case) and HADS Anxiety: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case).
• Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 12 months ]
  Hospital Anxiety and Depression Scale (HADS) was classified as follow: HADS for depression: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case) and HADS Anxiety: 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case).
• The The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) [ Time Frame: 3 months ]
  The PCL-5 is a self-report measure that assesses the presence and severity of Post Traumatic Stress Disorder (PTSD) symptoms. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. PTSD >32 is strongly associated with the presence of PTSD.
• The The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) [ Time Frame: 6 months ]
  The PCL-5 is a self-report measure that assesses the presence and severity of Post Traumatic Stress Disorder (PTSD) symptoms. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. PTSD >32 is strongly associated with the presence of PTSD.
• The The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) [ Time Frame: 12 months ]
  The PCL-5 is a self-report measure that assesses the presence and severity of Post Traumatic Stress Disorder (PTSD) symptoms. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. PTSD >32 is strongly associated with the presence of PTSD.
• Insomnia Severity Index (ISI) [ Time Frame: 3 months ]
  Insomnia Severity Index (ISI) is a brief instrument that was designed to assess the severity of both nighttime and daytime components of insomnia. It is available in several languages and is increasingly used as a metric of treatment response in clinical research. ISI will be classified as follows: No clinically significant insomnia (0-7), Subthreshold insomnia (8-14), Moderate insomnia (15-21), and severe insomnia (22-28).
• Insomnia Severity Index (ISI) [ Time Frame: 6 months ]
  Insomnia Severity Index (ISI) is a brief instrument that was designed to assess the severity of both nighttime and daytime components of insomnia. It is available in several languages and is increasingly used as a metric of treatment response in clinical research. ISI will be classified as follows: No clinically significant insomnia (0-7), Subthreshold insomnia (8-14), Moderate insomnia (15-21), and severe insomnia (22-28).
• Insomnia Severity Index (ISI) [ Time Frame: 12 months ]
  Insomnia Severity Index (ISI) is a brief instrument that was designed to assess the severity of both nighttime and daytime components of insomnia. It is available in several languages and is increasingly used as a metric of treatment response in clinical research. ISI will be classified as follows: No clinically significant insomnia (0-7), Subthreshold insomnia (8-14), Moderate insomnia (15-21), and severe insomnia (22-28).
• The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [ Time Frame: 3 months ]
  The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) is a widely used and extensively validated generic QOL measure that consists of 8 multiple-item domains. We applied two different methods for scoring. Firstly, for each item, a scale between 0-100 will be calculated and the percentage of predicted value has been calculated, based on the Italian normalized value. The second method will be been the calculation ofthe physical component summary (PCS) and the mental component summary (MCS), as described by Taft et al. After the eight scale scores are calculated, a z-score is determined for each by subtracting the scale mean of a sample of the Italian general population from an individual's scale score and then dividing by the standard deviation from the Italian general population. Each of the eight z-scores is then multiplied by the corresponding factor scoring coefficient for the scale.
• The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [ Time Frame: 6 months ]
  The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) is a widely used and extensively validated generic QOL measure that consists of 8 multiple-item domains. We applied two different methods for scoring. Firstly, for each item, a scale between 0-100 will be calculated and the percentage of predicted value has been calculated, based on the Italian normalized value. The second method will be been the calculation ofthe physical component summary (PCS) and the mental component summary (MCS), as described by Taft et al. After the eight scale scores are calculated, a z-score is determined for each by subtracting the scale mean of a sample of the Italian general population from an individual's scale score and then dividing by the standard deviation from the Italian general population. Each of the eight z-scores is then multiplied by the corresponding factor scoring coefficient for the scale.
• The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [ Time Frame: 12 months ]
  The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) is a widely used and extensively validated generic QOL measure that consists of 8 multiple-item domains. We applied two different methods for scoring. Firstly, for each item, a scale between 0-100 will be calculated and the percentage of predicted value has been calculated, based on the Italian normalized value. The second method will be been the calculation ofthe physical component summary (PCS) and the mental component summary (MCS), as described by Taft et al. After the eight scale scores are calculated, a z-score is determined for each by subtracting the scale mean of a sample of the Italian general population from an individual's scale score and then dividing by the standard deviation from the Italian general population. Each of the eight z-scores is then multiplied by the corresponding factor scoring coefficient for the scale.
• Barthel Index (BI) [ Time Frame: 3 months ]
  BI will be classified as follow: Independent (80-100); Minimally dependent (60-79);, Partially dependent (40-59), Very dependent (20-39); and Totally dependent (<20).
• Barthel Index (BI) [ Time Frame: 6 months ]
  BI will be classified as follow: Independent (80-100); Minimally dependent (60-79);, Partially dependent (40-59), Very dependent (20-39); and Totally dependent (<20).
• Barthel Index (BI) [ Time Frame: 12 months ]
  BI will be classified as follow: Independent (80-100); Minimally dependent (60-79);, Partially dependent (40-59), Very dependent (20-39); and Totally dependent (<20).

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Follow up in Survivors of Critical Illness
• Official Title: Long-term Follow-up in Survivors of Critical Illness: An Longitudinal Assessment of Critically Ill Patients Discharged Alive From the Intensive Care Unit

Brief Summary

Survivors of critical illness may suffer from persistent physical, cognitive and mental impairments, such as muscle weakness, dysfunction in the memory and executive domains, post-traumatic stress disorders, depression, and anxiety. This syndrome is referred to as Post Intensive Care Syndrome (PICS).

This study aims to assess the frequency of impairments, their evolution over time, and to understand the pathogenetic mechanisms and the association between long-term sequelae and acute care events.

Detailed Description

PICS describes 'new or worsening impairments in physical, cognitive or mental health status arising after critical illness and persisting beyond acute care hospitalization'. Different critical care professional and scientific societies have identified long-term functional outcomes after critical illness as an important target for research and clinical improvements, and there is general agreement that research on PICS should be a priority for the critical care community.

Post-ICU subjects may experience physical problems, such as muscles weakness and wasting, caused by prolonged bed rest and immobility during the ICU stay and by critical illness polyneuropathy and myopathy developing during the acute illness; organ dysfunction; chronic pain; mental health problems including depression, anxiety or post-traumatic stress disorder (PTSD); and neurocognitive impairments which are predominantly represented by memory dysfunction and executive function impairment. The impact of these problems on the subject's health status is huge, which reduced quality of life, and impaired functional status, and daily functioning.

Many survivors incur substantial healthcare costs, lose employment, and find their social networks wholly changed. The costs to subjects and families are high: ICU survivorship is associated with decreased return to work, and the loss of earnings plagues both patients and caregivers.

Prior studies in which researchers have examined outcomes among ICU survivors have been mainly restricted their assessments to specific patient populations and have used only limited outcome measures or the follow-up period was relatively short-term. Moreover, few studies have explored the association between acute care events and long-term sequelae as well as the underlying pathophysiological mechanisms.

The researchers appertaining to the present study implemented a follow-up clinic to describe the frequency of physical, cognitive, and mental impairments and their evolution over time in subjects surviving critical illness. The researchers also aim at understanding the pathogenetic mechanisms underlying these impairments and their association with acute care events.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: We will enroll all patients admitted to the ICUs with SARS-CoV-2 pneumonia and ARDS.
• Condition: Post Intensive Care Unit Syndrome
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Latronico N, Peli E, Calza S, Rodella F, Novelli MP, Cella A, Marshall J, Needham DM, Rasulo FA, Piva S; LOTO Investigators. Physical, cognitive and mental health outcomes in 1-year survivors of COVID-19-associated ARDS. Thorax. 2022 Mar;77(3):300-303. doi: 10.1136/thoraxjnl-2021-218064. Epub 2021 Sep 29.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 23, 2020): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2021
• Estimated Primary Completion Date: June 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

- All COVID-19 patients admitted to the ICUs of the Spedali Civili University Hospital in Brescia, Italy.

Exclusion Criteria:

- None

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04608994
• Other Study ID Numbers: NP2595
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No IPD will be shared

• Current Responsible Party: Piva Simone, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Original Responsible Party: Same as current
• Current Study Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Original Study Sponsor: Same as current
• Collaborators: Università degli Studi di Brescia
• Investigators: Not Provided
• PRS Account: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Verification Date: October 2020