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

Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03852537
• Other study ID #: 18-010925
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2019
• Est. completion date: November 17, 2020

Study information

• Verified date: September 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: November 17, 2020
• Est. primary completion date: November 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia

Intervention

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

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

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing	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)	Within 30 days of enrollment in study.
Secondary	Mortality	Number of subject deaths	90 days
Secondary	Need for High Flow Nasal Cannula Oxygen	Number of subjects to need high flow nasal cannula oxygen	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Need for Noninvasive Mechanical Ventilation	Assessed by the number of participants that required noninvasive mechanical ventilation.	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Need for Invasive Mechanical Ventilation	Assessed by the number of participants that required invasive mechanical ventilation.	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Organ Failure	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.	Measured daily for approximately 5 days
Secondary	New Onset Cardiac Arrhythmias	Number of participants who develop arrhythmias identified by electrocardiogram or echocardiogram.	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Myocardial Injury	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	Up to day +14 following study enrollment.
Secondary	Cardiovascular Dysfunction	Number of subjects with new and/or worsening right ventricle (RV)/left ventricle (LV) dysfunction	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Occurrence of Hyperglycemia	Number of participants who have hyperglycemia while receiving corticosteroids. Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.	Up to day +5 following study enrollment.
Secondary	Occurrence of Delirium	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.	Up to day +5 following study enrollment.
Secondary	Occurrence of Secondary Infection	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.	Up to day +14 following study enrollment.
Secondary	ICU Admission	Number of subjects admitted to the ICU	Within hospitalization or 30 days of study enrollment (whichever is sooner)
Secondary	Oxygen-free Days	Number of days subjects did not require oxygen assistance.	Within hospitalization or 30 days of study enrollment (whichever is sooner)

External Links

•   Mayo Clinic Clinical Trials