Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis Associated With Acute Necrotizing Soft Tissue Infections, The NASTI HAT Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Hospital Survival
研究概览
简要总结
Evaluate the impact of HAT therapy versus placebo in the treatment of patients with an acute NSTI and sepsis.
详细描述
Primary outcome:
- Hospital survival
Secondary outcomes:
-
Duration of vasopressor therapy
-
Requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI)
-
ICU length of stay (LOS)
-
Change in serum procalcitonin (PCT) over first 72 hours
-
Change in SOFA score over first 72 hours (measured as SOFA score daily for four days, with day one being admission, then 3 days after, totaling 4 days of treatment with HAT)
-
Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100)
-
Number of wound related surgeries
-
Wound status at time of hospital discharge:
-
Open
-
Closed
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
A randomization list will be used to show whether patients will be in group A or B. Only the Research Scientist who made the randomization list and the Pharmacy will know what group patients are in. The Burn Program Coordinator will get consent and enroll patients to the study. After that, the Burn Program Coordinator will call the pharmacy and report what group the patient is enrolled in, A or B. Then, the pharmacy will order the respective medications.
The doctors and nurses providing care for the patients will not know who is in what treatment group, and neither will the patients.
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
- •Necrotizing soft tissue infection by clinical diagnosis and requiring surgical treatment.
- •Sepsis by clinical diagnosis and/or by Sepsis-3 criteria15, with source attributed to the wound.
- •Anticipated or confirmed intensive care unit
排除标准
- •(Adapted from Sevransky et. al's VICTAS protocol)
- •Age < 18 years of age
- •Weight < 40 kg
- •Prior enrollment in this study or current enrollment in another study of any kind
- •Surgical findings, pathology/histology findings, or other findings determined to be inconsistent with an infectious acute NSTI such that the clinical diagnosis is no longer that of a NSTI
- •Sepsis deemed unlikely
- •Limitations of care during enrollment [defined as refusal of cardiovascular and respiratory support modes described in inclusion criteria, including "do not intubate" (DNI) status and comfort care]
- •Known allergy or known contraindication to vitamin C, thiamine, or corticosteroids [including previous history or active diagnosis of primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion, or known glucose-6-phosphate dehydrogenase (G6PD) deficiency]
- •Use of vitamin C at a dose of >1g/day (IV or oral) within the 24 hours preceding first episode of qualifying organ dysfunction during a given Emergency Department or Intensive Care Unit admission
- •Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g., stage IV malignancy, neurodegenerative disease, etc.)
- •Kidney Stone(s) of any kind
- •History of Oxalate Kidney Stone(s)
- •Pregnancy or known active breastfeeding
- •Prisoner or Incarceration
- •Inability or unwillingness of subject or legal surrogate/representative to give written informed consent
研究组 & 干预措施
Treatment Arm
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
- 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
- 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
- 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
干预措施: HAT (Drug)
Control Arm
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
干预措施: Placebo (Drug)
结局指标
主要结局
Hospital Survival
时间窗: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.
Hospital survival is a binary variable showing whether the patient survived their time in the hospital. Hospital survival will be assessed from date of randomization until the date of discharge or date of death from any cause, whichever comes first, assessed up to 24 months.
次要结局
- Duration of Vasopressor Therapy(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- Requirement for Renal Replacement Therapy in Patients With Acute Kidney Injury (AKI)(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- ICU Length of Stay (LOS)(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- Change in Serum Procalcitonin (PCT) Over First 72 Hours(Over the first 72 hours from admission.)
- Change in Sequential Organ Failure Assessment (SOFA) Score Over First 72 Hours (Measured as SOFA Score Daily for Four Days, With Day One Being Admission, Then 3 Days After, Totaling 4 Days of Treatment With HAT)(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- Procalcitonin Clearance(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- Number of Wound Related Surgeries(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)
- Wound Status at Time of Hospital Discharge: Open(Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.)