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Recruiting NCT06818266

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

Phase III Interventional Sickle Cell Disease Acute Chest Syndrome

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Tocilizumab (RoActemra®, 20 mg/mL)., Placebo (NaCl 0.9%).
Who it may be relevant to
Registry conditions: Sickle Cell Disease, Acute Chest Syndrome. Basic parameters: from 2 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning from both supplemental oxygen and any respiratory support, in pediatric and adult patients with sickle cell disease (SCD) during acute chest syndrome (ACS).

Detailed description

SCD is a severe hemoglobinopathy, considered the first monogenic disease in the world. ACS, one of the most frequent and serious complications of SCD, is the first cause of hospitalization and mortality of SCD patients in intensive care unit. However, its pathophysiology has long been poorly understood and therapeutic options are limited.

A major increase has been recently reported in the level of interleukin-6 (IL-6), unlike other main pro-inflammatory cytokines, in the sputum (or bronchoalveolar fluid) from SCD children during ACS, positively correlated with the severity of ACS. Also, the observations of a very rapidly favorable outcome after administration of tocilizumab (anti-human IL-6 receptor monoclonal antibody) in SCD patients hospitalized for ACS with or without SARS-CoV-2 infection, suggest that tocilizumab may be a key therapy for ACS.

Interventions

  • Drug Tocilizumab (RoActemra®, 20 mg/mL).
    One single intravenous infusion at 8 mg/kg (up to a maximum of 800 mg) for patients ≥ 30 kg and 12 mg/kg for patients \< 30 kg
  • Drug Placebo (NaCl 0.9%)
    One single intravenous infusion

Primary outcome measures

  • Time to successful weaning from both supplemental oxygen and any respiratory support [Time frame: During hospitalization for ACS, from randomization until day 28 after randomization]
Secondary outcome measures (12)
  • Adverse events during hospitalization and within 3 months following tocilizumab or placebo injection [Time frame: Within 3 months after randomization]
  • Time to discharge [Time frame: From the date of randomization until the date of end of hospitalization, assessed up to 3 months]
  • Mortality [Time frame: Within 3 months after randomization]
  • Need for transfusion [Time frame: From the date of randomization until the date of end of hospitalization, assessed up to 3 months]
  • Total number of red blood cell units received [Time frame: From the date of randomization until the date of end of hospitalization, assessed up to 3 months]
  • Need for non-invasive ventilation (for patients without ventilatory support at inclusion) [Time frame: From the date of randomization until the date of end of hospitalization, assessed up to 3 months]
  • Need for invasive ventilation (for patients without invasive ventilation at inclusion) [Time frame: From the date of randomization until the date of end of hospitalization, assessed up to 3 months]
  • Readmission for vaso-occlusive crisis or ACS within 3 months following tocilizumab or placebo injection [Time frame: Within 3 months after randomization]
  • C-reactive protein (CRP), procalcitonin (PCT), plasma and sputum IL-6 levels 48 (+/- 12) hours after tocilizumab or placebo injection [Time frame: 48 (+/- 12) hours after tocilizumab or placebo injection]
  • Procalcitonin (PCT) level 48 (+/- 12) hours after tocilizumab or placebo injection [Time frame: 48 (+/- 12) hours after tocilizumab or placebo injection]
  • Plasma IL-6 level 48 (+/- 12) hours after tocilizumab or placebo injection [Time frame: 48 (+/- 12) hours after tocilizumab or placebo injection]
  • Sputum IL-6 level 48 (+/- 12) hours after tocilizumab or placebo injection [Time frame: 48 (+/- 12) hours after tocilizumab or placebo injection]

Eligibility criteria

Inclusion criteria

  • SCD patient of all genotypes (SS, SC, S/β0 and S/β+ or other major SCD syndrome)
  • Age ≥ 2 years old
  • 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)
  • 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
  • Negative pregnancy test for girls or women of childbearing age
  • Freely given, informed and written consent of patient or legal representatives
  • Affiliation to the social security (or health insurance)
  • Effective contraception up to 3 months after the administration of treatment (tocilizumab or placebo)

Exclusion criteria

  • Impossibility to perform tocilizumab/placebo injection within the first 48 hours of supplemental oxygen ≥2L/min for SpO2≥95% 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.
  • Known hypersensitivity to tocilizumab or its excipients
  • 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)
  • Immunization with a live/attenuated vaccine within the last 4 weeks
  • Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies and investigational agents within the last 3 months
  • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • 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
  • Evidence of malignant disease or malignancies diagnosed within the last 3 years
  • Pregnancy or breastfeeding
  • Imminent and inevitable progression towards death in the opinion of the investigator
  • Absolute neutrophil count < 1.0 G/L or platelets < 50 G/L
  • ALT or AST > 5-fold the upper limit of normal
  • Glomerular Filtration rate (GFR) < 60 mL/min/1,73 m²
  • Current enrolment in another interventional research concerning a medicinal product for human use

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

France · 1 center
  • Department of General Pediatrics and Sickle Cell Center, Necker-Enfants malades Hospital — Paris

Identifiers

NCT: NCT06818266 · APHP220797 · 2023-505109-17-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗