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

NCT03852537 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 18-010925
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumonia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Mortality

  90 days

• Need for High Flow Nasal Cannula Oxygen

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

• Need for Noninvasive Mechanical Ventilation

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

• Need for Invasive Mechanical Ventilation

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

• Organ Failure

  Measured daily for approximately 5 days

Study Arms (2)

Usual Care

ACTIVE COMPARATOR

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

Other: Usual Care

Biomarker-adjusted Steroid Dosing

EXPERIMENTAL

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

Interventions

Methylprednisolone DRUG

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

Also known as: Biomarker guided steroid dosing

Biomarker-adjusted Steroid Dosing

Usual Care OTHER

Usual care as determined by the patients treatment team.

Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to hospital with community acquired pneumonia.
• Acute respiratory failure SpO2/FiO2 \< 315 (SpO2\<90% on room air or \<97% on 2L NC).

You may not qualify if:

• 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:
• 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).
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 34983600 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Pneumonia; COVID-19

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Hemang Yadav, MBBS, MS
• Organization: Mayo Clinic

Yadav.Hemang@mayo.edu

507-266-3958

Study Officials

• Hemang Yadav

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 25, 2019
• Study Start: December 2, 2019
• Primary Completion: November 17, 2020
• Study Completion: November 17, 2020
• Last Updated: September 16, 2021
• Results First Posted: September 16, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From 9 months to 36 months after article publication.

Locations

US (1)