Tocilizumab Acute Chest

Sponsor

University of Chicago (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05640271

Collaborator

(none)

200

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

We 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, we are hopeful that this will be an effective strategy. We 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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Acute Chest Syndrome	Drug: Tocilizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Treatment

Official Title:

Low-Dose Tocilizumab for Acute Chest Syndrome in Sickle Cell Disease

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tocilizumab Tocilizumab 80 mg IV dose (one time per patient)
Active Comparator: 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.	Drug: Tocilizumab Tocilizumab 80 mg IV dose (one time per patient)

Arm

Intervention/Treatment

Experimental: 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.

Drug: Tocilizumab

Tocilizumab 80 mg IV dose (one time per patient)

Active Comparator: 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.

Drug: Tocilizumab

Tocilizumab 80 mg IV dose (one time per patient)

Outcome Measures

Primary Outcome Measures

Time-weighted SaO2/FiO2 ratio [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults ≥ 18 years of age
Prior diagnosis of sickle cell disease (Hb SS, Hb SC, Hb Sb+, and Hb Sb0)
Admission in the past 5 years to the University of Chicago for acute chest syndrome (IRB21-2036) with outpatient hematologist agreement to screen, enrollment in the University of Chicago Sickle Cell Registry (16607A), or current admission to the University of Chicago for acute chest syndrome. Although patients with an admission in the past 5 years or on the Sickle Cell Registry will be registered and consented in the outpatient setting, randomization will only occur when a subject is admitted for ACS.

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Chicago

Investigators

Study Director: Austin Wesevich, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Chicago

ClinicalTrials.gov Identifier:

NCT05640271

Other Study ID Numbers:

IRB22-0277

First Posted:

Dec 7, 2022

Last Update Posted:

Dec 7, 2022

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Acute Chest Syndrome

Anemia, Sickle Cell

Syndrome

Study Results

No Results Posted as of Dec 7, 2022