PneumoniaPhase 2NCT03852537
Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
A Phase 2 study testing Methylprednisolone in people with Pneumonia, run by Mayo Clinic at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumonia
- What is being tested?
- Methylprednisolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2019to 17 Nov 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted to hospital with community acquired pneumonia.
- Acute respiratory failure SpO2/FiO2 < 315 (SpO2<90% on room air or <97% on 2L NC).
- 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).
Who cannot join
- 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
Show all 20Show fewer
- 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:
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
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.
Read the 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.
- Conditions
- Pneumonia
- Being tested
- Methylprednisolone, Usual Care
- Keywords
- Pneumonia, steroid, COVID-19, SARS CoV-2
- Medical subject headings
- Pneumonia, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Biomarker guided steroid dosing
Methylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'.
Usual CareOther
Usual care as determined by the patients treatment team.
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | Active comparator | Usual care as determined by the patient's primary team. Receives: 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). Receives: Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Within 30 days of enrollment in study.
Secondary outcomes (13)
Mortality
Number of subject deaths
Measured: 90 days
Need for High Flow Nasal Cannula Oxygen
Number of subjects to need high flow nasal cannula oxygen
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Need for Noninvasive Mechanical Ventilation
Assessed by the number of participants that required noninvasive mechanical ventilation.
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Need for Invasive Mechanical Ventilation
Assessed by the number of participants that required invasive mechanical ventilation.
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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: Measured daily for approximately 5 days
New Onset Cardiac Arrhythmias
Number of participants who develop arrhythmias identified by electrocardiogram or echocardiogram.
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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
Measured: Up to day +14 following study enrollment.
Cardiovascular Dysfunction
Number of subjects with new and/or worsening right ventricle (RV)/left ventricle (LV) dysfunction
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
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.
Measured: Up to day +5 following study enrollment.
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.
Measured: Up to day +5 following study enrollment.
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.
Measured: Up to day +14 following study enrollment.
ICU Admission
Number of subjects admitted to the ICU
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Oxygen-free Days
Number of days subjects did not require oxygen assistance.
Measured: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2019
- Study start2 Dec 2019
- Primary completion17 Nov 2020
- Study completion17 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hemang Yadav, Mayo Clinic
- Investigators
- Hemang Yadav, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03852537
- Sponsor's protocol ID
- 18-010925
- Status last verified
- Sep 2021
- First submitted
- 15 Feb 2019
- Last updated
- 16 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34983600
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
- ClinicalTrials.gov ID
- NCT03852537
- Acronym / sponsor ID
- 18-010925
- Conditions
- Pneumonia
- Keywords
- Pneumonia, steroid, COVID-19, SARS CoV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 2 Dec 2019 (actual)
- Primary completion
- 17 Nov 2020 (actual)
- Study completion
- 17 Nov 2020 (actual)
- First posted
- 25 Feb 2019 (actual)
- Results
- Posted 16 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Usual Care | Active comparator | Other: Usual CareUsual care as determined by the patient's primary team. |
| Biomarker-adjusted Steroid Dosing | Experimental | Drug: MethylprednisoloneIndividualized, 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients admitted to hospital with community acquired pneumonia.
- Acute respiratory failure SpO2/FiO2 < 315 (SpO2<90% on room air or <97% on 2L NC).
- 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).
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneAlso: Biomarker guided steroid dosingMethylprednisolone will be administered based on CRP-guided protocol outlined under 'Biomarker-adjusted steroid dosing'. | Drug | Biomarker-adjusted Steroid Dosing |
| Usual CareUsual care as determined by the patients treatment team. | Other | Usual Care |
Primary outcome
Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
Time frame: Within 30 days of enrollment in study.
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)
13 secondary outcomes
Mortality
Time frame: 90 days
Need for High Flow Nasal Cannula Oxygen
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Need for Noninvasive Mechanical Ventilation
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Need for Invasive Mechanical Ventilation
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Organ Failure
Time frame: Measured daily for approximately 5 days
New Onset Cardiac Arrhythmias
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Myocardial Injury
Time frame: Up to day +14 following study enrollment.
Cardiovascular Dysfunction
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Occurrence of Hyperglycemia
Time frame: Up to day +5 following study enrollment.
Occurrence of Delirium
Time frame: Up to day +5 following study enrollment.
Occurrence of Secondary Infection
Time frame: Up to day +14 following study enrollment.
ICU Admission
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Oxygen-free Days
Time frame: Within hospitalization or 30 days of study enrollment (whichever is sooner)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34983600Odeyemi 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.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hemang Yadav principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylprednisolone in people with Pneumonia, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing (time frame: Within 30 days of enrollment in study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03852537, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.