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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03852537
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Hemang Yadav, Mayo Clinic

Brief Summary:

In community acquired pneumonia, corticosteroids have been shown to have potential benefit. However, the limited and variable use of adjunctive corticosteroids in critically ill patients is largely due to an inability to identify patients that will benefit from the use of anti-inflammatory medications. This study compares usual care to a novel biomarker-tailored steroid dosing algorithm for patients with community acquired pneumonia.

In April 2020, in response to the SARS CoV-2 pandemic, we added a COVID-19 arm to this study. The study will evaluate the role of biomarker-titrated adjuvant corticosteroid administration compared to usual care in patients admitted to hospital with SARS CoV-2 (COVID-19) infection and acute respiratory failure.


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, 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)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
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
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

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'.




Primary Outcome Measures :
  1. Feasibility of the timely initiation of corticosteroids and implementation of biomarker-titrated corticosteroid dosing: percentage of eligible patients adhered to the timely initiation [ Time Frame: Within 30 days of enrollment in study. ]
    A percentage of eligible patients adhered to the timely initiation (within 12 hours of emergency room admission) and daily corticosteroid treatment according to ESICM/SCCM clinical practice guideline (control group) or biomarker concordance (intervention group)


Secondary Outcome Measures :
  1. Mortality [ Time Frame: Within 30 days and 90 days of study enrollment ]
    Death from any cause

  2. Progression of disease [ Time Frame: Within hospitalization or 30 days of study enrollment (whichever is sooner) ]
    Progression of disease is defined by the need for high flow nasal cannula oxygen, noninvasive or invasive ventilation. Given the proliferation of high flow nasal cannula oxygen use in lieu of mechanical ventilation, instead of ventilator-free days the investigators opt for using advanced respiratory support free days where "advanced respiratory support" includes both invasive and noninvasive mechanical ventilation and the high flow nasal cannula oxygen.

  3. Evolution of respiratory failure [ Time Frame: Within 72 hours of enrollment in study. ]
    Measured by respiratory component of SOFA at time of ICU admission, after 24 hours, after 48 hours and after 72 hours and by the organ failure free days. In the absence of daily arterial blood gas analysis, PaO2/FiO2 ratio will be replaced by SpO2/FiO2 ratio

  4. Evolution of kidney failure [ Time Frame: Within 72 hours of enrollment in study. ]
    Assessed by renal component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no renal failure and 4 indicating severe renal failure).

  5. Evolution of shock [ Time Frame: Within 72 hours of enrollment in study. ]
    Assessed by cardiac component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no cardiovascular failure and 4 indicating severe cardiovascular failure).

  6. Length of stay [ Time Frame: From time of study enrollment up to discharge from hospital, to a maximum of 1 year. ]
    In hospital and in ICU

  7. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: 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.

  8. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: 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.

  9. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: 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.



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 (SaO2/FiO2 < 315 or PaO2/FiO2 < 300).

Exclusion Criteria:

  • 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 90 days
  • Suspected flare of Interstitial lung disease (infectious and non-infectious)

For the COVID-19 arm of the study:

Inclusion criteria:

  • Patients admitted to hospital with COVID-19 pneumonia (confirmed by positive SARS CoV-2 testing).
  • Acute respiratory failure (SaO2/FiO2 < 315 or PaO2/FiO2 < 300).

Exclusion critieria:

  • Same as pneumonia arm above.

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 Recruiting
Rochester, Minnesota, United States, 55905
Contact: Amy L Amsbaugh    507-255-5123    amsbaugh.amy@mayo.edu   
Principal Investigator: Hemang Yadav         
Sponsors and Collaborators
Mayo Clinic
Investigators
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Principal Investigator: Hemang Yadav Mayo Clinic
Additional Information:
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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
Last Update Posted: April 22, 2020
Last Verified: April 2020

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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
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
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