Low-Dose Tocilizumab for Acute Chest Syndrome in Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Time-weighted SaO2/FiO2 ratio
研究概览
简要总结
The investigators are evaluating the role of a low dose of tocilizumab in treating acute chest syndrome in patients with sickle cell disease. Tocilizumab inhibits interleukin-6 (IL-6) receptors and is used to treat rheumatoid arthritis and severe cytokine release syndrome, which can be seen with chimeric antigen receptor T-cell (CAR-T) therapy, and it is also authorized for treatment of COVID-19. Since IL-6 levels are elevated in the sputum of patients with acute chest syndrome, the investigators are hopeful that this will be an effective strategy. The investigators will be looking at how a low dose of tocilizumab affects oxygen status, clinical outcomes, and laboratory markers in patients admitted to the hospital with acute chest syndrome.
详细描述
In this randomized, placebo-controlled, double-blinded phase II study, enrolled patients admitted to the University of Chicago who are diagnosed with acute chest syndrome will receive one dose of tocilizumab 80 mg IV and one normal saline placebo dose. The order of these doses will be randomized at a 1:1 ratio. After collecting oxygenation data as a baseline for 8 hours, patients will then receive tocilizumab versus placebo as their early dose and then the opposite (placebo versus tocilizumab) 48 hours later. Clinical, laboratory, and patient-reported outcome data will be collected during their admission and compared between arms.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study statistician will generate randomizations using the method of permuted block randomization. The pharmacy will access the prepared randomization list via REDCap (a module separate from the clinical REDCap database) to guide tocilizumab versus placebo administration at the time of placing an inpatient order. Prior to randomization, the SpO2 to FiO2 ratio will be determined over an 8-hour period to serve as a baseline measure. Thus, randomization will be done at the time of placing the initial order for inpatient tocilizumab versus placebo, not at the time of enrollment. Patients, study investigators, and inpatient clinicians will all be blinded to the patient's randomized group assignment. Only the investigational pharmacy will be aware of the randomization arm.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 12 years of age
- •Prior diagnosis of sickle cell disease (Hb SS, Hb SC, Hb Sb+, and Hb Sb0)
排除标准
- •Pregnant patients or breastfeeding mothers.
- •Prior treatment with gene therapy or a stem cell transplant.
- •Current enrollment in a clinical trial involving an FDA-regulated drug or biologic.
- •Current neutropenia (absolute neutrophil count < 1000/mm^3)
- •Current thrombocytopenia (platelet count < 50,000 mm^3)
- •Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 10 times the upper limit of normal (ULN)
- •History of tuberculosis (TB).
- •Positive purified protein derivative (PPD) TB screening test.
- •On active therapy with a Bruton's tyrosine kinase-targeted agent, which include the following: Acalabrutinib, Ibrutinib, Zanubrutinib
- •On active therapy with a JAK2-targeted agent, which include the following: Baricitinib, Ruxolitinib, Tofacitinib, Upadacitinib
- •Any of the following biologic immunosuppressive agent (and any biosimilar versions thereof) administered in the past 6 months:
- •Abatacept, Adalimumab, Alemtuzumab, Atezolizumab, Belimumab, Blinatumomab, Brentuximab, Certolizumab, Daratumumab, Durvalumab, Eculizumab, Elotuzumab, Etanercept, Gemtuzumab, Golimumab, Ibritumomab, Infliximab, Inotuzumab, Ipilimumab, Ixekizumab, Moxetumomab, Nivolumab, Obinutuzumab, Ocrelizumab, Ofatumumab, Pembrolizumab, Polatuzumab, Rituximab, Sarilumab, Secukinumab, Tocilizumab, Tositumumab, Tremelimumab, Urelumab, Ustekinumab
研究组 & 干预措施
Early Tocilizumab
This arm will receive tocilizumab 80 mg at the time of acute chest syndrome diagnosis and subsequent randomization. Then, two days later, they will receive 50 mL of normal saline.
干预措施: Tocilizumab (Drug)
Delayed Tocilizumab
This arm will receive 50 mL of normal saline at the time of acute chest syndrome diagnosis and subsequent randomization. Then, two days later, they will receive tocilizumab 80 mg. Thus, this delayed arm will serve as a placebo comparator for the first 48 hours and then as an active comparator for the remaining duration on study.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Time-weighted SaO2/FiO2 ratio
时间窗: Total of 4 days (Day 0 to Day 4)
Oxygenation data will be obtained as part of routine clinical care. All changes in pulse oximetry measurement that are documented in the chart will be recorded in an oxygen saturation case report form with the date and time from Day 0 to Day 4. These peripheral oxygen saturation (SpO2) measurements will serve as surrogates for SaO2. Additionally, all changes in the route of supplemental oxygen delivery, rate of supplemental oxygen delivery, and fraction of inspired oxygen (FiO2) will be recorded in a corresponding case report form with the date and time from Day 0 to Day 4. The time-weighted SaO2/FiO2 ratio, our primary endpoint, will be calculated based on these two case report forms.
次要结局
- Length of stay(Up to 3 months (Admission Date to Discharge Date))
- Mortality rate(Total of 29 days (Day 0 to Day 28))
- Readmission rate(Total of 29 days (Discharge Date to 28 days after discharge))
- Red cell exchange transfusion rate(Total of 9 days (Day 0 to Day 8))
- Intensive Care Unit (ICU) transfer rate(Total of 9 days (Day 0 to Day 8))