Low-dose Tocilizumab Versus Standard of Care in Hospitalized Patients With COVID-19
Status:
Recruiting
Trial end date:
2021-03-01
Target enrollment:
Participant gender:
Summary
COVID-19's high mortality may be driven by hyperinflammation. Interleukin-6 (IL-6) axis
therapies may reduce COVID-19 mortality. Retrospective analyses of tocilizumab in severe to
critical COVID-19 patients have demonstrated survival advantage and lower likelihood of
requiring invasive ventilation following tocilizumab administration. The majority of patients
have rapid resolution (i.e., within 24-72 hours following administration) of both clinical
and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single
tocilizumab dose.
The investigators hypothesized that a dose of tocilizumab significantly lower than the EMA-
and FDA-labeled dose (8mg/kg) as well as the emerging standard of care dose (400mg) may be
effective in patients with COVID-19 pneumonitis and hyperinflammation. Advantages to the
lower dose of tocilizumab may include lower likelihood of secondary bacterial infections as
well as extension of this drug's limited supply. The investigators conducted an adaptive
single-arm phase 2 trial (NCT04331795) evaluating clinical and biochemical response to
low-dose tocilizumab in patients with COVID-19 pneumonitis and hyperinflammation.
This multi-center, prospective, randomized controlled phase 2 trial -- designed as two
sub-studies to allow for the possible emergence of data demonstrating the clinical efficacy
of tocilizumab 8mg/kg or 400mg -- formally tests the clinical efficacy of low-dose
tocilizumab in COVID-19 pneumonia.
Sub-Study A Primary Objective A: To establish whether low-dose tocilizumab reduces the time
to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation, when
compared to a tocilizumab-free standard of care.
Hypothesis A: The investigators hypothesize that low-dose tocilizumab, when compared to a
tocilizumab-free standard of care, decreases the time to recovery in hospitalized,
non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation by three
days or more.
Sub-Study B Primary Objective B: To establish whether low-dose tocilizumab is near-equivalent
to high-dose tocilizumab (400mg or 8 mg/kg) in reducing the time to clinical recovery in
patients with COVID-19 pneumonitis and hyperinflammation.
Hypothesis B: The investigators hypothesize that low-dose tocilizumab is near-equivalent to
high-dose tocilizumab in reducing the time to clinical recovery in hospitalized,
non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation.