Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.
J Transl Med
; 18(1): 405, 2020 10 21.
Статья
в английский
| MEDLINE | ID: covidwho-1477432
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
BACKGROUND:
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.METHODS:
A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.RESULTS:
In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI 13.6-24.0, P = 0.52) and 22.4% (97.5% CI 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.CONCLUSIONS:
Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).ключевые слова
Полный текст:
Имеется в наличии
Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Pneumonia, Viral
/
Coronavirus Infections
/
Antibodies, Monoclonal, Humanized
/
Betacoronavirus
Тип исследования:
Когортное исследование
/
Экспериментальные исследования
/
Наблюдательное исследование
/
Прогностическое исследование
/
Рандомизированные контролируемые испытания
Пределы темы:
Взрослые
/
Пожилые
/
Женщины
/
Люди
/
Мужчины
/
Middle aged
Страна как тема:
Европа
Язык:
английский
Журнал:
J Transl Med
Год:
2020
Тип:
Статья
Аффилированная страна:
S12967-020-02573-9
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