Objective and design
The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19.
Subjects
The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia.
Treatment
206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy.
Methods
The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders.
Results
63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups.
Conclusion
In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate.
Trail registration
The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).
Takotsubo syndrome (TTS) is a reversible left ventricular dysfunction characterized by local apical hypokinesia usually triggered by a physical or emotional stress. According to the last available data TTS may represent 2% of all admissions for acute coronary syndromes. Despite the reliable prevalence, diagnosis of TTS remains difficult. The initial presentation, both clinically and electrocardiographically, is similar to an acute myocardial infarction (AMI). The biomarker profile is also similar, although the peaks of troponin and creatinine kinase levels are lower, and brain natriuretic peptide levels are higher in patients with TTS compared with ST-segment elevation AMI. Modified Mayo diagnostic criteria are the most common for the diagnosis. Pathogenesis of TTS currently is not well understood. Catecholamines appear to play a central role in the pathophysiology of TTS. However, it is conceivable that some people have a genetic predisposition to stress-induced TTS. A genetic predisposition has been suggested based on the few familial TTS cases described. Despite reversible myocardial dysfunction, acute heart failure is the most common complication in the acute phase of TTS. In-hospital mortality rate is comparable to that of ST-segment elevation AMI. There are no randomized clinical trials to support specific treatment recommendations in TTS. It is believed that the tactics of managing patients with TTS hospitalized with suspicion of acute coronary syndrome should comply with the protocol of management of patients with AMI while acute coronary pathology is not excluded.
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