SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients admitted to hospital with community acquired pneumonia.
- •Acute respiratory failure SpO2/FiO2 < 315 (SpO2<90% on room air or <97% on 2L NC).
排除标准
- •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
研究组 & 干预措施
Usual Care
Usual care as determined by the patient's primary team.
干预措施: Usual Care (Other)
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).
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Timely Initiation of Corticosteroids and Implementation of Biomarker-titrated Corticosteroid Dosing
时间窗: 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)
次要结局
- 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)
- New Onset Cardiac Arrhythmias(Within hospitalization or 30 days of study enrollment (whichever is sooner))
- Occurrence of Delirium(Up to day +5 following study enrollment.)
- Occurrence of Secondary Infection(Up to day +14 following study enrollment.)
- Myocardial Injury(Up to day +14 following study enrollment.)
- Cardiovascular Dysfunction(Within hospitalization or 30 days of study enrollment (whichever is sooner))
- Occurrence of Hyperglycemia(Up to day +5 following study enrollment.)
- ICU Admission(Within hospitalization or 30 days of study enrollment (whichever is sooner))
- Oxygen-free Days(Within hospitalization or 30 days of study enrollment (whichever is sooner))