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

Primary Purpose

Pneumonia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Methylprednisolone

Usual Care

About this trial

This is an interventional treatment trial for Pneumonia focused on measuring Pneumonia, steroid, COVID-19, SARS CoV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Usual Care

Biomarker-adjusted Steroid Dosing

Arm Description

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

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).

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Mortality

Number of subject deaths

Need for High Flow Nasal Cannula Oxygen

Number of subjects to need high flow nasal cannula oxygen

Need for Noninvasive Mechanical Ventilation

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

Need for Invasive Mechanical Ventilation

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

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.

New Onset Cardiac Arrhythmias

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

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

Cardiovascular Dysfunction

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

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.

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.

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.

ICU Admission

Number of subjects admitted to the ICU

Oxygen-free Days

Number of days subjects did not require oxygen assistance.

Full Information

NCT ID

NCT03852537

First Posted

February 15, 2019

Last Updated

September 12, 2021

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT03852537

Brief Title

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

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

December 2, 2019 (Actual)

Primary Completion Date

November 17, 2020 (Actual)

Study Completion Date

November 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pneumonia

Keywords

Pneumonia, steroid, COVID-19, SARS CoV-2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Usual Care

Arm Type

Active Comparator

Arm Description

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

Arm Title

Biomarker-adjusted Steroid Dosing

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Methylprednisolone

Other Intervention Name(s)

Biomarker guided steroid dosing

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Usual Care

Intervention Description

Usual care as determined by the patients treatment team.

Primary Outcome Measure Information:

Title

Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing

Description

Time Frame

Within 30 days of enrollment in study.

Secondary Outcome Measure Information:

Title

Mortality

Description

Number of subject deaths

Time Frame

90 days

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)

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)

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)

Title

Organ Failure

Description

Time Frame

Measured daily for approximately 5 days

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)

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.

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)

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.

Title

Occurrence of Delirium

Description

Time Frame

Up to day +5 following study enrollment.

Title

Occurrence of Secondary Infection

Description

Time Frame

Up to day +14 following study enrollment.

Title

ICU Admission

Description

Number of subjects admitted to the ICU

Time Frame

Within hospitalization or 30 days of study enrollment (whichever is sooner)

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hemang Yadav

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

From 9 months to 36 months after article publication.

Citations:

PubMed Identifier

34983600

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.

Results Reference

derived

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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

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