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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03852537
Recruitment Status : Completed
First Posted : February 25, 2019
Results First Posted : September 16, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Hemang Yadav, Mayo Clinic

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
Pneumonia Drug: Methylprednisolone Other: Usual Care 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.

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Study Type : Interventional  (Clinical Trial)
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 : December 2, 2019
Actual Primary Completion Date : November 17, 2020
Actual Study Completion Date : November 17, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

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 Name: Biomarker guided steroid dosing




Primary Outcome Measures :
  1. Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing [ Time Frame: 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 [ Time Frame: 90 days ]
    Number of subject deaths

  2. Need for High Flow Nasal Cannula Oxygen [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner) ]
    Number of subjects admitted to the ICU

  13. Oxygen-free Days [ Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner) ]
    Number of days subjects did not require oxygen assistance.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03852537


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
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Principal Investigator: Hemang Yadav Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Hemang Yadav, Mayo Clinic:
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hemang Yadav, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03852537    
Other Study ID Numbers: 18-010925
First Posted: February 25, 2019    Key Record Dates
Results First Posted: September 16, 2021
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in any manuscript resulting from this research, after deidentification (text, tables, figures, and appendices) and the study protocol will be shared beginning 9 months and ending 36 months following article publication, to anyone who wishes to access the data. Proposals should be directed to yadav.hemang@mayo.edu. To gain access, data requestors will need to sign a data access agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: From 9 months to 36 months after article publication.

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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, Mayo Clinic:
Pneumonia, steroid, COVID-19, SARS CoV-2
Additional relevant MeSH terms:
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Pneumonia
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents