Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT03852537
Collaborator
(none)
44
1
2
11.5
3.8

Study Details

Study Description

Brief Summary

This research study is being done to determine the appropriate dose of steroids and the appropriate duration for steroid use to reduce inflammation in severe pneumonia needing a form of breathing support. This study seeks to compare usual care to a unique (individualized) dosing strategy. A marker of inflammation in the body will be measured in blood samples. This marker of inflammation is called C- reactive protein. The overall goal is to identify patients that will benefit most from steroid use and decrease use of steroids. The information collected from this study may provide information that may improve management of patients with severe pneumonia requiring a form of breathing support.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a two-arm single-center pilot phase II clinical trial. Patients will be screened at the time of hospital admission and will be required to be enrolled within the clinical trial within 48 hours of hospital admission.

In the individualized, biomarker-concordant arm, all patients will receive steroids once at the time of admission, then a daily morning dose. In order to account for varying turnaround time at different laboratories, C-Reactive Protein (CRP) levels will be drawn with early morning labs, and used to determine the steroid dosing for the day. Patients will receive daily CRP measurements for the first 5 days of the hospitalization, or until hospital discharge. CRP measurements will be discontinued once the CRP is less than 50mmol/L.

Steroid administration will be facilitated using standardized computerized physician order entry. The patients, treating physicians and outcome assessors will be blinded to the group assignment. Steroid order sets will include 6 hourly point of care glucose monitoring, and an insulin sliding scale for glucose levels to facilitate glucose management. The need for insulin drip will be determined by the treating physician. Additional testing including serum and urine ketones will be informed by the glucose level, serum anion gap and bicarbonate levels in routine basic metabolic panels and determined by the treating physician.

In the usual care arm, patients will receive daily CRP measurements for the first 5 days of the hospitalization, or until hospital discharge.

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
Actual Study Start Date :
Dec 2, 2019
Actual Primary Completion Date :
Nov 17, 2020
Actual Study Completion Date :
Nov 17, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Usual Care

Usual care as determined by the patient's primary team.

Other: Usual Care
Usual care as determined by the patients treatment team.

Experimental: Biomarker-adjusted Steroid Dosing

Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone).

Drug: Methylprednisolone
Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
Other Names:
  • Biomarker guided steroid dosing
  • Outcome Measures

    Primary Outcome Measures

    1. Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing [Within 30 days of enrollment in study.]

      Number of eligible subjects to adhered to the timely initiation and daily corticosteroid treatment according to ESICM/Society of Critical Care Medicine SCCM clinical practice guideline (control group) or biomarker concordance (intervention group)

    Secondary Outcome Measures

    1. Mortality [90 days]

      Number of subject deaths

    2. Need for High Flow Nasal Cannula Oxygen [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Number of subjects to need high flow nasal cannula oxygen

    3. Need for Noninvasive Mechanical Ventilation [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Assessed by the number of participants that required noninvasive mechanical ventilation.

    4. Need for Invasive Mechanical Ventilation [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Assessed by the number of participants that required invasive mechanical ventilation.

    5. Organ Failure [Measured daily for approximately 5 days]

      Organ failures measured by Sequential Organ Failure Assessment (SOFA). The overall score is based on 6 sub-scores respiratory system, neurologic system, cardiovascular system, hepatic system, coagulation, and renal system using an overall scale of 0-24, which 0=no organ failure, 24=complete organ failure.

    6. New Onset Cardiac Arrhythmias [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Number of participants who develop arrhythmias identified by electrocardiogram or echocardiogram.

    7. Myocardial Injury [Up to day +14 following study enrollment.]

      Number of participants with evidence of myocardial injury determined by daily troponin peak and /or new diagnosis of Left Ventricular (LV) dysfunction (LVEF <40%) or new diagnosis of cor pulmonale

    8. Cardiovascular Dysfunction [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Number of subjects with new and/or worsening right ventricle (RV)/left ventricle (LV) dysfunction

    9. Occurrence of Hyperglycemia [Up to day +5 following study enrollment.]

      Number of participants who have hyperglycemia while receiving corticosteroids. Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.

    10. Occurrence of Delirium [Up to day +5 following study enrollment.]

      Number of participants who develop delirium while receiving corticosteroids. Delirium will be assessed by Confusion Assessment Method for the ICU (CAM-ICU) measurement tool. The CAM-ICU is a binary (yes/no) scale for assessing the presence of delirium.

    11. Occurrence of Secondary Infection [Up to day +14 following study enrollment.]

      Number of participants who develop secondary infections during and after steroid therapy. A secondary infection is defined as a new infection that develops after initiation of corticosteroid therapy, until 5 days after steroids are discontinued.

    12. ICU Admission [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Number of subjects admitted to the ICU

    13. Oxygen-free Days [Within hospitalization or 30 days of study enrollment (whichever is sooner)]

      Number of days subjects did not require oxygen assistance.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    For the Pneumonia arm of the study:
    Inclusion Criteria:
    • Patients admitted to hospital with community acquired pneumonia.

    • Acute respiratory failure SpO2/FiO2 < 315 (SpO2<90% on room air or <97% on 2L NC).

    Exclusion Criteria:
    • Contraindications or unwilling to use steroids by patient or provider

    • Refractory septic shock defined as a requirement of norepinephrine dose or equivalent above >0.1 microgram/kilogram/minute or 2 or more vasopressors

    • Pre-admission chronic use of steroids or other immunosuppressive medications

    • Adrenal insufficiency

    • Comfort care

    • Leukopenia <1000/mm or neutropenia <500/mm (except if attributable to pneumonia) and HIV positive with a CD4 count <100

    • Recent or past history of bone marrow or solid organ transplantation

    • Hospital admission in the previous 30 days

    • Suspected flare of Interstitial lung disease (infectious and non-infectious)

    • Positive influenza testing or high suspicion for influenza

    For the COVID-19 arm of the study:
    Inclusion Criteria:
    • Patients admitted to hospital with COVID-19 pneumonia (high suspicion or confirmed by positive SARS CoV-2 testing).

    • Acute respiratory failure SpO2/FiO2 < 315 (SpO2<90% on room air or <97% on 2L NC).

    Exclusion Criteria:
    • Contraindications or unwilling to use steroids by patient or provider

    • Refractory septic shock defined as a requirement of norepinephrine dose or equivalent above >0.1 microgram/kilogram/minute or 2 or more vasopressors

    • Pre-admission chronic use of steroids or other immunosuppressive medications

    • Adrenal insufficiency

    • Comfort care

    • Leukopenia <1000/mm or neutropenia <500/mm (except if attributable to pneumonia) and HIV positive with a CD4 count <100

    • Recent or past history of bone marrow or solid organ transplantation

    • Suspected flare of Interstitial lung disease (infectious and non-infectious)

    • Positive influenza testing or high suspicion for influenza

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Principal Investigator: Hemang Yadav, Mayo Clinic

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Hemang Yadav, Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT03852537
    Other Study ID Numbers:
    • 18-010925
    First Posted:
    Feb 25, 2019
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Hemang Yadav, Principal Investigator, Mayo Clinic
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Period Title: Overall Study
    STARTED 23 21
    COMPLETED 23 21
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing Total
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'. Total of all reporting groups
    Overall Participants 23 21 44
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    60.0
    59.0
    60.0
    Sex: Female, Male (Count of Participants)
    Female
    9
    39.1%
    9
    42.9%
    18
    40.9%
    Male
    14
    60.9%
    12
    57.1%
    26
    59.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    8.7%
    0
    0%
    2
    4.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    2
    9.5%
    2
    4.5%
    White
    18
    78.3%
    17
    81%
    35
    79.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    3
    13%
    2
    9.5%
    5
    11.4%
    Region of Enrollment (participants) [Number]
    United States
    23
    100%
    21
    100%
    44
    100%

    Outcome Measures

    1. Primary Outcome
    Title Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
    Description Number of eligible subjects to adhered to the timely initiation and daily corticosteroid treatment according to ESICM/Society of Critical Care Medicine SCCM clinical practice guideline (control group) or biomarker concordance (intervention group)
    Time Frame Within 30 days of enrollment in study.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    20
    87%
    19
    90.5%
    2. Secondary Outcome
    Title Mortality
    Description Number of subject deaths
    Time Frame 90 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    1
    4.3%
    1
    4.8%
    3. Secondary Outcome
    Title Need for High Flow Nasal Cannula Oxygen
    Description Number of subjects to need high flow nasal cannula oxygen
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    7
    30.4%
    4
    19%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.494
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Need for Noninvasive Mechanical Ventilation
    Description Assessed by the number of participants that required noninvasive mechanical ventilation.
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    4
    17.4%
    2
    9.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.666
    Comments
    Method Fisher Exact
    Comments
    5. Secondary Outcome
    Title Need for Invasive Mechanical Ventilation
    Description Assessed by the number of participants that required invasive mechanical ventilation.
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    3
    13%
    2
    9.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Fisher Exact
    Comments
    6. Secondary Outcome
    Title Organ Failure
    Description Organ failures measured by Sequential Organ Failure Assessment (SOFA). The overall score is based on 6 sub-scores respiratory system, neurologic system, cardiovascular system, hepatic system, coagulation, and renal system using an overall scale of 0-24, which 0=no organ failure, 24=complete organ failure.
    Time Frame Measured daily for approximately 5 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Day 1
    3.0
    7.0
    Day 2
    3.0
    3.0
    Day 3
    3.0
    3.0
    Day 4
    3.0
    3.0
    Day 5
    3.0
    5.5
    7. Secondary Outcome
    Title New Onset Cardiac Arrhythmias
    Description Number of participants who develop arrhythmias identified by electrocardiogram or echocardiogram.
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    0
    0%
    1
    4.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.477
    Comments
    Method Fisher Exact
    Comments
    8. Secondary Outcome
    Title Myocardial Injury
    Description Number of participants with evidence of myocardial injury determined by daily troponin peak and /or new diagnosis of Left Ventricular (LV) dysfunction (LVEF <40%) or new diagnosis of cor pulmonale
    Time Frame Up to day +14 following study enrollment.

    Outcome Measure Data

    Analysis Population Description
    Data were missing for 8 subjects in the usual care arm and 4 subjects in the biomarker-adjusted steroid dosing arm.
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 15 17
    Count of Participants [Participants]
    8
    34.8%
    10
    47.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Chi-squared
    Comments
    9. Secondary Outcome
    Title Cardiovascular Dysfunction
    Description Number of subjects with new and/or worsening right ventricle (RV)/left ventricle (LV) dysfunction
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    1
    4.3%
    1
    4.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Fisher Exact
    Comments
    10. Secondary Outcome
    Title Occurrence of Hyperglycemia
    Description Number of participants who have hyperglycemia while receiving corticosteroids. Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.
    Time Frame Up to day +5 following study enrollment.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    11
    47.8%
    18
    85.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method Fisher Exact
    Comments
    11. Secondary Outcome
    Title Occurrence of Delirium
    Description Number of participants who develop delirium while receiving corticosteroids. Delirium will be assessed by Confusion Assessment Method for the ICU (CAM-ICU) measurement tool. The CAM-ICU is a binary (yes/no) scale for assessing the presence of delirium.
    Time Frame Up to day +5 following study enrollment.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    5
    21.7%
    5
    23.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Fisher Exact
    Comments
    12. Secondary Outcome
    Title Occurrence of Secondary Infection
    Description Number of participants who develop secondary infections during and after steroid therapy. A secondary infection is defined as a new infection that develops after initiation of corticosteroid therapy, until 5 days after steroids are discontinued.
    Time Frame Up to day +14 following study enrollment.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    0
    0%
    0
    0%
    13. Secondary Outcome
    Title ICU Admission
    Description Number of subjects admitted to the ICU
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Count of Participants [Participants]
    10
    43.5%
    5
    23.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Usual Care, Biomarker-adjusted Steroid Dosing
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments
    Method Chi-squared
    Comments
    14. Secondary Outcome
    Title Oxygen-free Days
    Description Number of days subjects did not require oxygen assistance.
    Time Frame Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    Measure Participants 23 21
    Median (Inter-Quartile Range) [days]
    21.0
    24.0

    Adverse Events

    Time Frame Adverse events were collected from baseline to end of study for a total of approximately 90 days on all participants.
    Adverse Event Reporting Description
    Arm/Group Title Usual Care Biomarker-adjusted Steroid Dosing
    Arm/Group Description Corticosteroid use and dosing determined by the patient's primary team for standard of care. Usual Care: Corticosteroid use and dosing determined by the patients treatment team for standard of care. Individualized, biomarker concordant steroid use: dosing, titration and duration according to CRP level. This is a predetermined dosing table that adjusts dose of steroid by CRP level. Specifically: if CRP < 50 mmol/L: discontinue steroid; if CRP is between 51-100 mmol/L: 0.5 mg methylprednisolone (or dose equivalent of oral prednisone); if CRP is between 101-150 mmol/L: 0.75 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level is between 151-200 mmol/L: 1 mg/kg methylprednisolone (or dose equivalent of oral prednisone); if CRP level > 200 mmol/L: 1.5 mg/kg methylprednisolone (or dose equivalent of oral prednisone). Methylprednisolone: Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
    All Cause Mortality
    Usual Care Biomarker-adjusted Steroid Dosing
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/23 (4.3%) 1/21 (4.8%)
    Serious Adverse Events
    Usual Care Biomarker-adjusted Steroid Dosing
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/21 (0%)
    Other (Not Including Serious) Adverse Events
    Usual Care Biomarker-adjusted Steroid Dosing
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/21 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Hemang Yadav, MBBS, MS
    Organization Mayo Clinic
    Phone 507-266-3958
    Email Yadav.Hemang@mayo.edu
    Responsible Party:
    Hemang Yadav, Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT03852537
    Other Study ID Numbers:
    • 18-010925
    First Posted:
    Feb 25, 2019
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021