Back to resultsTocilizumab for Acute Chest Syndrome
Primary Purpose
Sickle Cell Disease, Acute Chest Syndrome
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria: Adults ≥ 18 years of age Prior diagnosis of sickle cell disease (Hb SS, Hb SC, Hb Sb+, and Hb Sb0) Exclusion Criteria: Pregnant patients or breastfeeding mothers. 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
Sites / Locations
- University of ChicagoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Early Tocilizumab
Delayed Tocilizumab
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Time-weighted SaO2/FiO2 ratio
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.
Secondary Outcome Measures
Red cell exchange transfusion rate
As part of routine clinical care by the inpatient team, patients may receive a red cell exchange transfusion. The study team will assess if participants received any exchange transfusions from Day 0 to Day 8, and if so, they will record the date of the first exchange transfusion and the total number of units transfused during that time period.
Intensive Care Unit (ICU) transfer rate
Patients will be assessed for if they were admitted directly to the intensive care unit (ICU) or if they were transferred from the general medicine floor to the ICU between Day 0 and Day 8. The date of transfer to the ICU will be recorded if applicable.
Length of stay
Patients will be assessed for their admission and discharge dates. Length of stay will be calculated based on those two dates.
Readmission rate
Patients will be assessed for readmission for 28 days from discharge. Readmission will be assessed at the University of Chicago as well as through any linked hospitals through Care Everywhere within the electronic medical record system. The date of readmission will be recorded if applicable.
Mortality rate
Patients will be assessed for mortality from Day 0 to Day 28. The date of death will be recorded if applicable.
Full Information
NCT ID
NCT05640271
First Posted
November 28, 2022
Last Updated
August 8, 2023
Sponsor
University of Chicago
1. Study Identification
Unique Protocol Identification Number
NCT05640271
Brief Title
Tocilizumab for Acute Chest Syndrome
Official Title
Low-Dose Tocilizumab for Acute Chest Syndrome in Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 10, 2023 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Acute Chest Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
All participants will receive tocilizumab 80 mg on one day and placebo (normal saline 50 mL) on another day, separated by 48 hours, and the order of these two doses will be randomized. Half the patients will receive tocilizumab at the time of acute chest syndrome diagnosis and subsequent randomization, and then that half will receive placebo two days later. The other half will receive placebo first and then tocilizumab two days later.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Early Tocilizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Delayed Tocilizumab
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Tocilizumab 80 mg IV dose (one time per patient)
Primary Outcome Measure Information:
Title
Time-weighted SaO2/FiO2 ratio
Description
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.
Time Frame
Total of 4 days (Day 0 to Day 4)
Secondary Outcome Measure Information:
Title
Red cell exchange transfusion rate
Description
As part of routine clinical care by the inpatient team, patients may receive a red cell exchange transfusion. The study team will assess if participants received any exchange transfusions from Day 0 to Day 8, and if so, they will record the date of the first exchange transfusion and the total number of units transfused during that time period.
Time Frame
Total of 9 days (Day 0 to Day 8)
Title
Intensive Care Unit (ICU) transfer rate
Description
Patients will be assessed for if they were admitted directly to the intensive care unit (ICU) or if they were transferred from the general medicine floor to the ICU between Day 0 and Day 8. The date of transfer to the ICU will be recorded if applicable.
Time Frame
Total of 9 days (Day 0 to Day 8)
Title
Length of stay
Description
Patients will be assessed for their admission and discharge dates. Length of stay will be calculated based on those two dates.
Time Frame
Up to 3 months (Admission Date to Discharge Date)
Title
Readmission rate
Description
Patients will be assessed for readmission for 28 days from discharge. Readmission will be assessed at the University of Chicago as well as through any linked hospitals through Care Everywhere within the electronic medical record system. The date of readmission will be recorded if applicable.
Time Frame
Total of 29 days (Discharge Date to 28 days after discharge)
Title
Mortality rate
Description
Patients will be assessed for mortality from Day 0 to Day 28. The date of death will be recorded if applicable.
Time Frame
Total of 29 days (Day 0 to Day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults ≥ 18 years of age
Prior diagnosis of sickle cell disease (Hb SS, Hb SC, Hb Sb+, and Hb Sb0)
Exclusion Criteria:
Pregnant patients or breastfeeding mothers.
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Austin Wesevich, MD
Phone
773-834-6732
Email
austin.wesevich@uchicagomedicine.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Austin Wesevich, MD
Organizational Affiliation
University of Chicago
Official's Role
Study Director
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Austin Wesevich, MD
Phone
773-834-6732
Email
austin.wesevich@uchicagomedicine.org
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Tocilizumab for Acute Chest Syndrome
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