Clinical trial NCT03852537: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
Official title: SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pneumonia
Keywords: Pneumonia, steroid, COVID-19, SARS CoV-2
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2019-02-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
timeFrame: Within 30 days of enrollment in study.
Secondary outcomes:
measure: Mortality
timeFrame: 90 days
measure: Need for High Flow Nasal Cannula Oxygen
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Need for Noninvasive Mechanical Ventilation
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Need for Invasive Mechanical Ventilation
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Organ Failure
timeFrame: Measured daily for approximately 5 days
measure: New Onset Cardiac Arrhythmias
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Myocardial Injury
timeFrame: Up to day +14 following study enrollment.
measure: Cardiovascular Dysfunction
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Occurrence of Hyperglycemia
timeFrame: Up to day +5 following study enrollment.
measure: Occurrence of Delirium
timeFrame: Up to day +5 following study enrollment.
measure: Occurrence of Secondary Infection
timeFrame: Up to day +14 following study enrollment.
measure: ICU Admission
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
measure: Oxygen-free Days
timeFrame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Hemang Yadav
role: PRINCIPAL_INVESTIGATOR
References:
citation: Odeyemi YE, Chalmers SJ, Barreto EF, Jentzer JC, Gajic O, Yadav H. Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial. Crit Care. 2022 Jan 4;26(1):9. doi: 10.1186/s13054-021-03873-2.