<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04412330</url>
  </required_header>
  <id_info>
    <org_study_id>59097</org_study_id>
    <nct_id>NCT04412330</nct_id>
  </id_info>
  <brief_title>Optimizing Outcomes With Physical Therapy Treatment for IndividuALs Surviving an ICU Admission for Covid-19</brief_title>
  <acronym>OPTIMAL</acronym>
  <official_title>Optimizing Outcomes With Physical Therapy Treatment for IndividuALs Surviving an ICU Admission for Covid-19 (OPTImAL) - a Single Center Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Kentucky</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ashley Montgomery-Yates</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction: Survivors of acute respiratory failure develop persistent muscle weakness and&#xD;
      deficits in cardiopulmonary endurance combining to limit physical functioning. Early data&#xD;
      from the Covid-19 pandemic suggest a high incidence of critically ill patients admitted to&#xD;
      intensive care units (ICU) will require mechanical ventilation for acute respiratory failure.&#xD;
      Covid-19 patients surviving an admission to the ICU are expected to suffer from physical and&#xD;
      cognitive impairments that will limit quality of life and return to pre-hospital level of&#xD;
      functioning. In this present study, the investigators will evaluate the safety and&#xD;
      feasibility of providing a novel clinical pathway combining ICU after-care at an ICU Recovery&#xD;
      clinic with physical therapy interventions.&#xD;
&#xD;
      Methods and Analysis: In this single-center, prospective (pre, post cohort) trial in patients&#xD;
      surviving ICU admission for Covid-19. The investigators hypothesize that this novel&#xD;
      combination is a) safe and feasible to provide for patients surviving Covid-19; b) improve&#xD;
      physical function and exercise capacity measured by performance on 6-minute walk test and&#xD;
      Short Performance Physical battery; and c) reduce incidence of anxiety, depression and&#xD;
      post-traumatic stress assessed with Hospital Anxiety and Depression Scale and the Impact of&#xD;
      Events Scale-revised. Safety will be assessed by pooled adverse events and reason for early&#xD;
      termination of interventions. Feasibility will be assessed by rate of adherence and&#xD;
      attrition. Repeated measures ANOVA will be utilized to assess change in outcomes from at&#xD;
      first ICU Recovery Clinic follow-up (2-weeks) and 3- and 6-months post hospital discharge.&#xD;
&#xD;
      Ethics and Dissemination: The trial has received ethics approval at the University of&#xD;
      Kentucky and enrollment has begun. The results of this trial will support the feasibility of&#xD;
      providing ICU follow-up and physical therapy interventions for patients surviving critical&#xD;
      illness for Covid-19 and may begin to support effectiveness of such interventions.&#xD;
      Investigators plan to disseminate trial results in peer-reviewed journals, as well as&#xD;
      presentation at physical therapy and critical care national and international conferences.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ICU Recovery Clinic is standard of care for patients surviving a critical illness in the&#xD;
      Medical ICU at the University of Kentucky. The ICU Recovery Clinic includes a&#xD;
      transdisciplinary team with input from five disciplines that provide coordinated outpatient&#xD;
      care with a focus on medical issues, medication management, nutrition, sleep disruption, and&#xD;
      any issues related to post-intensive care syndrome such as anxiety, depression, PTSD,&#xD;
      cognitive dysfunction and physical impairments.&#xD;
&#xD;
      Individualized physical therapy treatment: After the initial ICU recovery clinic appointment&#xD;
      patients will begin their 8-week physical therapy program which will be delivered 1-2 times&#xD;
      per week in a supervised 1:1 session and supplemented with 3 days of unsupervised home&#xD;
      exercises and walking program on days not participating in physical therapy sessions.&#xD;
      Supervised sessions will be run by a physical therapist (&gt;20 years of experience in ICU and&#xD;
      pulmonary rehabilitation) either face to face in outpatient setting or through telemedicine&#xD;
      using video consultation platforms for patients unable to attend appointments due to&#xD;
      transmission risk, transportation issues, or geographically living &gt;45 miles from clinic.&#xD;
      Prior to commencing the first treatment session patients will complete baseline testing to&#xD;
      inform the starting parameters (frequency, intensity, repetitions) based on performance in&#xD;
      physical tests such as 6MWT and muscle strength testing. The patient will receive an&#xD;
      individualized and tailored physical therapy treatment, which will be targeted towards&#xD;
      increasing their aerobic fitness, muscle strength and functional ability.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Actual">May 5, 2021</completion_date>
  <primary_completion_date type="Actual">May 5, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Prospective study with one-treatment arm</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events (safety)</measure>
    <time_frame>through study completion, an average of 3-months</time_frame>
    <description>Incidence of adverse events, quantified by pain or discomfort that causes termination of interventions; a fall (with or without injury) during interventions or directly related to interventions such as fall due to fatigue; and physiologic event/abnormality that warrants termination of interventions or medical follow-up including bradycardia, tachycardia, and emergent hypertension</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility (success of consent process, adherence, and attrition)</measure>
    <time_frame>through study completion, an average of 3-months</time_frame>
    <description>Feasibility will be assessed by the consent rate (number of patients agreed to participate/number of patients approached for consent) and adherence attendance measured by the percentage of sessions patient participated divided total number of scheduled appointments. Adherence will also be prospectively assessed by total duration of exercise, dosage and intensity of exercises as described above. Attrition will be quantified by number of patients lost to follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six minute walk test</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Distance walked on six-minute walk test performed in line with the ATS/ERS Guidelines as measure of exercise capacity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Performance Physical Battery</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Short Performance Physical Battery (SPPB) is a performance-based physical function test with components of balance, repetitive five times sit-to-stand for time, and 4-meter habitual gait speed. Higher scores on SPPB indicate better physical function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (EQ-5DL)</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Health-related quality of life (HRQoL) will be measured by self-report questionnaire, the Five Dimension Euro-Quality of Life (EQ-5D) that includes a visual analog scale with rating for overall HRQoL (0-100)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Cognitive function will be assessed by the Montreal Cognitive Assessment (MOCA) with &lt;23/30 distinguishing mild cognitive impairment. If the patient participating in telemedicine through Zoom then the MOCA-Blind version will be completed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and Depression</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Anxiety and depression will be assessed with the Hospital Anxiety and Depression Scale (HADS), a fourteen-item scale with subset scores of &gt;8/21 indicating anxiety or depression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTSD and distress</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>Distress and Post-traumatic stress disorder (PTSD) will be assessed through the Impact of Events Scale-Revised (IES-R), a 22-item self-report measure, with scores &gt;35/88 recommending provisional diagnosis of PTSD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Return to work</measure>
    <time_frame>Assessed at baseline, and repeated 3- and 6-months post hospital discharge</time_frame>
    <description>For patients previously employed, the return to work will be assessed using the self-report survey instrument designed for ICU follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary complication</measure>
    <time_frame>Assessed 3 and 6-months post hospital discharge</time_frame>
    <description>Readmission rate and morality with be assessed</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Covid-19</condition>
  <condition>Critical Illness</condition>
  <condition>Post Intensive Care Unit Syndrome</condition>
  <condition>Muscle Weakness</condition>
  <arm_group>
    <arm_group_label>ICU followup + physical therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients surviving ICU admission for Covid-19 will receive ICU follow-up care in an ICU Recovery Clinic plus 8 weeks of physical therapy interventions. ICU Recovery Clinic is standard of care for patients surviving medical ICU admission at University of Kentucky with potential to attend in person or complete through telemedicine up to 5 appointments in the first year after hospital discharge. Physical therapy interventions completed at an outpatient pulmonary rehabilitation center or through telemedicine is not currently standard of care for patients in the short-term recovery phase (1-6 months after hospital discharge) after critical illness.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ICU Recovery + Physical Therapy</intervention_name>
    <description>Physical therapy interventions will be supervised by a physical therapist (&gt;20 years of experience in ICU and pulmonary rehabilitation). Potential interventions include endurance/aerobic training (treadmill training, upper and lower extremity ergometer, and recumbent step machine), upper and lower extremity resistance strength training, balance training, functional movement training, and education. If the interventions are providing in the home environment the exercises will be completed through Zoom, video communications app. Home-based interventions will include seated and standing exercise including resistance exercises (such as lifting small weights) and endurance (e.g. marching or stepping in place, repetitive sit-to-stand training). Physical therapist will provide verbal instructions for motivation and adherence to exercise interventions.</description>
    <arm_group_label>ICU followup + physical therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (&gt;18 years of age) surviving an ICU admission with laboratory confirmed&#xD;
             Covid-19.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pre-existing neurological or orthopedic injury, disease, or condition that would&#xD;
             prevent participation in exercise interventions.&#xD;
&#xD;
          -  patient not ambulatory prior to hospitalization&#xD;
&#xD;
          -  patient not expected to survivor 90 days after hospitalization&#xD;
&#xD;
          -  pregnant&#xD;
&#xD;
          -  prisoner&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kirby P Mayer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>May 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 8, 2021</last_update_submitted>
  <last_update_submitted_qc>June 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Kirby Mayer</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Muscle Weakness</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04412330
org study id: 59097
nct id: NCT04412330
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Introduction: Survivors of acute respiratory failure develop persistent muscle weakness and
      deficits in cardiopulmonary endurance combining to limit physical functioning. Early data
      from the Covid-19 pandemic suggest a high incidence of critically ill patients admitted to
      intensive care units (ICU) will require mechanical ventilation for acute respiratory failure.
      Covid-19 patients surviving an admission to the ICU are expected to suffer from physical and
      cognitive impairments that will limit quality of life and return to pre-hospital level of
      functioning. In this present study, the investigators will evaluate the safety and
      feasibility of providing a novel clinical pathway combining ICU after-care at an ICU Recovery
      clinic with physical therapy interventions.

      Methods and Analysis: In this single-center, prospective (pre, post cohort) trial in patients
      surviving ICU admission for Covid-19. The investigators hypothesize that this novel
      combination is a) safe and feasible to provide for patients surviving Covid-19; b) improve
      physical function and exercise capacity measured by performance on 6-minute walk test and
      Short Performance Physical battery; and c) reduce incidence of anxiety, depression and
      post-traumatic stress assessed with Hospital Anxiety and Depression Scale and the Impact of
      Events Scale-revised. Safety will be assessed by pooled adverse events and reason for early
      termination of interventions. Feasibility will be assessed by rate of adherence and
      attrition. Repeated measures ANOVA will be utilized to assess change in outcomes from at
      first ICU Recovery Clinic follow-up (2-weeks) and 3- and 6-months post hospital discharge.

      Ethics and Dissemination: The trial has received ethics approval at the University of
      Kentucky and enrollment has begun. The results of this trial will support the feasibility of
      providing ICU follow-up and physical therapy interventions for patients surviving critical
      illness for Covid-19 and may begin to support effectiveness of such interventions.
      Investigators plan to disseminate trial results in peer-reviewed journals, as well as
      presentation at physical therapy and critical care national and international conferences.
ICU Recovery Clinic is standard of care for patients surviving a critical illness in the
      Medical ICU at the University of Kentucky. The ICU Recovery Clinic includes a
      transdisciplinary team with input from five disciplines that provide coordinated outpatient
      care with a focus on medical issues, medication management, nutrition, sleep disruption, and
      any issues related to post-intensive care syndrome such as anxiety, depression, PTSD,
      cognitive dysfunction and physical impairments.

      Individualized physical therapy treatment: After the initial ICU recovery clinic appointment
      patients will begin their 8-week physical therapy program which will be delivered 1-2 times
      per week in a supervised 1:1 session and supplemented with 3 days of unsupervised home
      exercises and walking program on days not participating in physical therapy sessions.
      Supervised sessions will be run by a physical therapist (>20 years of experience in ICU and
      pulmonary rehabilitation) either face to face in outpatient setting or through telemedicine
      using video consultation platforms for patients unable to attend appointments due to
      transmission risk, transportation issues, or geographically living >45 miles from clinic.
      Prior to commencing the first treatment session patients will complete baseline testing to
      inform the starting parameters (frequency, intensity, repetitions) based on performance in
      physical tests such as 6MWT and muscle strength testing. The patient will receive an
      individualized and tailored physical therapy treatment, which will be targeted towards
      increasing their aerobic fitness, muscle strength and functional ability.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Prospective study with one-treatment arm
measure: Adverse events (safety)
time frame: through study completion, an average of 3-months
description: Incidence of adverse events, quantified by pain or discomfort that causes termination of interventions; a fall (with or without injury) during interventions or directly related to interventions such as fall due to fatigue; and physiologic event/abnormality that warrants termination of interventions or medical follow-up including bradycardia, tachycardia, and emergent hypertension
measure: Feasibility (success of consent process, adherence, and attrition)
time frame: through study completion, an average of 3-months
description: Feasibility will be assessed by the consent rate (number of patients agreed to participate/number of patients approached for consent) and adherence attendance measured by the percentage of sessions patient participated divided total number of scheduled appointments. Adherence will also be prospectively assessed by total duration of exercise, dosage and intensity of exercises as described above. Attrition will be quantified by number of patients lost to follow-up.
measure: Six minute walk test
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Distance walked on six-minute walk test performed in line with the ATS/ERS Guidelines as measure of exercise capacity
measure: Short Performance Physical Battery
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Short Performance Physical Battery (SPPB) is a performance-based physical function test with components of balance, repetitive five times sit-to-stand for time, and 4-meter habitual gait speed. Higher scores on SPPB indicate better physical function.
measure: Quality of life (EQ-5DL)
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Health-related quality of life (HRQoL) will be measured by self-report questionnaire, the Five Dimension Euro-Quality of Life (EQ-5D) that includes a visual analog scale with rating for overall HRQoL (0-100)
measure: Cognitive function
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Cognitive function will be assessed by the Montreal Cognitive Assessment (MOCA) with <23/30 distinguishing mild cognitive impairment. If the patient participating in telemedicine through Zoom then the MOCA-Blind version will be completed.
measure: Anxiety and Depression
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Anxiety and depression will be assessed with the Hospital Anxiety and Depression Scale (HADS), a fourteen-item scale with subset scores of >8/21 indicating anxiety or depression
measure: PTSD and distress
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: Distress and Post-traumatic stress disorder (PTSD) will be assessed through the Impact of Events Scale-Revised (IES-R), a 22-item self-report measure, with scores >35/88 recommending provisional diagnosis of PTSD
measure: Return to work
time frame: Assessed at baseline, and repeated 3- and 6-months post hospital discharge
description: For patients previously employed, the return to work will be assessed using the self-report survey instrument designed for ICU follow-up
measure: Secondary complication
time frame: Assessed 3 and 6-months post hospital discharge
description: Readmission rate and morality with be assessed
arm group label: ICU followup + physical therapy
arm group type: Experimental
description: Patients surviving ICU admission for Covid-19 will receive ICU follow-up care in an ICU Recovery Clinic plus 8 weeks of physical therapy interventions. ICU Recovery Clinic is standard of care for patients surviving medical ICU admission at University of Kentucky with potential to attend in person or complete through telemedicine up to 5 appointments in the first year after hospital discharge. Physical therapy interventions completed at an outpatient pulmonary rehabilitation center or through telemedicine is not currently standard of care for patients in the short-term recovery phase (1-6 months after hospital discharge) after critical illness.
intervention type: Other
intervention name: ICU Recovery + Physical Therapy
description: Physical therapy interventions will be supervised by a physical therapist (>20 years of experience in ICU and pulmonary rehabilitation). Potential interventions include endurance/aerobic training (treadmill training, upper and lower extremity ergometer, and recumbent step machine), upper and lower extremity resistance strength training, balance training, functional movement training, and education. If the interventions are providing in the home environment the exercises will be completed through Zoom, video communications app. Home-based interventions will include seated and standing exercise including resistance exercises (such as lifting small weights) and endurance (e.g. marching or stepping in place, repetitive sit-to-stand training). Physical therapist will provide verbal instructions for motivation and adherence to exercise interventions.
arm group label: ICU followup + physical therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kirby P Mayer, PhD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Kentucky
investigator full name: Kirby Mayer
investigator title: Assistant Professor
mesh term: COVID-19
mesh term: Muscle Weakness
mesh term: Critical Illness
sharing ipd: No