- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03852537
Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Usual Care
Usual care as determined by the patient's primary team.
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Usual care as determined by the patients treatment team.
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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).
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Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
Time Frame: Within 30 days of enrollment in study.
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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)
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Within 30 days of enrollment in study.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: 90 days
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Number of subject deaths
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90 days
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Need for High Flow Nasal Cannula Oxygen
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Number of subjects to need high flow nasal cannula oxygen
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Need for Noninvasive Mechanical Ventilation
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Assessed by the number of participants that required noninvasive mechanical ventilation.
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Need for Invasive Mechanical Ventilation
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Assessed by the number of participants that required invasive mechanical ventilation.
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Organ Failure
Time Frame: Measured daily for approximately 5 days
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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.
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Measured daily for approximately 5 days
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New Onset Cardiac Arrhythmias
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Number of participants who develop arrhythmias identified by electrocardiogram or echocardiogram.
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Myocardial Injury
Time Frame: Up to day +14 following study enrollment.
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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
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Up to day +14 following study enrollment.
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Cardiovascular Dysfunction
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Number of subjects with new and/or worsening right ventricle (RV)/left ventricle (LV) dysfunction
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Occurrence of Hyperglycemia
Time Frame: Up to day +5 following study enrollment.
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Number of participants who have hyperglycemia while receiving corticosteroids.
Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.
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Up to day +5 following study enrollment.
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Occurrence of Delirium
Time Frame: Up to day +5 following study enrollment.
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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.
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Up to day +5 following study enrollment.
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Occurrence of Secondary Infection
Time Frame: Up to day +14 following study enrollment.
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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.
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Up to day +14 following study enrollment.
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ICU Admission
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Number of subjects admitted to the ICU
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Oxygen-free Days
Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Number of days subjects did not require oxygen assistance.
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Within hospitalization or 30 days of study enrollment (whichever is sooner)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hemang Yadav, Mayo Clinic
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Pneumonia
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
Other Study ID Numbers
- 18-010925
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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