Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Patients With Sickle Cell Disease

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Feb 4, 2025

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness and safety of a medication called tocilizumab for treating acute chest syndrome in patients with sickle cell disease. Acute chest syndrome is a serious condition that can cause breathing difficulties and is often treated in the hospital. The goal of the trial is to see if a single dose of tocilizumab can help patients breathe better and reduce the time they need to rely on oxygen or other breathing support.

To be eligible for this trial, participants must be at least 2 years old and have sickle cell disease. They need to be hospitalized with acute chest syndrome and require extra oxygen or breathing assistance. The trial is open to both children and adults, regardless of the specific type of sickle cell disease they have. If chosen to participate, patients will receive either tocilizumab or a placebo (a substance with no active ingredients) and will be monitored for their breathing improvement. It's important to note that certain health conditions may exclude individuals from participating in the trial, and all participants must provide informed consent to join.

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Eligibility criteria

• Inclusion Criteria:
• • 1. SCD patient of all genotypes (SS, SC, S/β0 and S/β+)
• • 2. Age ≥ 2 years old
• • 3. Hospitalized for ACS, defined by the WHO as the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging, (X-ray, lung ultrasound, or CT scan)
• • 4. Requiring supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95% or non-invasive respiratory support (high flow nasal oxygen or continuous positive airway pressure or bilevel non-invasive ventilation) or invasive mechanical ventilation or ECMO, for less than 48 hours
• • 5. Negative pregnancy test for girls or women of childbearing age
• • 6. Freely given, informed and written consent of patient or legal representatives
• • 7. Affiliation to the social security (or health insurance)
• • 8. Effective contraception up to 3 months after the administration of treatment (tocilizumab or placebo)
• Exclusion Criteria:
• • 1. Impossibility to perform tocilizumab/placebo injection within the first 48 hours of supplemental oxygen and/or respiratory support (as defined in inclusion criteria n°4). If exchange transfusion is indicated at inclusion, it has to be performed before the injection of tocilizumab/placebo.
• • 2. Known hypersensitivity to tocilizumab or its excipients
• • 3. Known active current severe bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster)
• • 4. Immunization with a live/attenuated vaccine within the last 4 weeks
• • 5. Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies and investigational agents within the last 3 months
• • 6. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• • 7. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions that might predispose a patient to perforations
• • 8. Evidence of malignant disease or malignancies diagnosed within the last 3 years
• • 9. Pregnancy or breastfeeding
• • 10. Imminent and inevitable progression towards death in the opinion of the investigator
• • 11. Absolute neutrophil count \< 1.0 G/L or platelets \< 50 G/L
• • 12. ALT or AST \> 5-fold the upper limit of normal
• • 13. Glomerular Filtration rate (GFR) \< 60 mL/min/1,73 m²
• • 14. Current enrolment in another interventional research concerning a medicinal product for human use