Methylprednisolone pulses plus tacrolimus in addition to standard of care vs. standard of care alone in patients with severe COVID-19. A randomized controlled trial
Author
Solanich, Xavier
Antolí, Arnau
Rocamora-Blanch, Gemma
Padullés, Núria
Fanlo-Maresma, Marta
Iriarte, Adriana
Mitjavila, Francesca
Capdevila, Olga
Riera-Mestre, Antoni
Bas, Jordi
Vicens-Zygmunt, Vanesa
Niubó, Jordi
Calvo, Nahum
Bolivar, Santiago
Rigo-Bonnin, Raúl
Mensa-Vilaró, Anna
Arregui, Laura
Tebé, Cristian
Videla, Sebastià
Hereu, Pilar
Corbella Virós, Xavier
Publication date
2021ISSN
2095-0217
Abstract
Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39–1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360–842] vs. 870 mg [IQR 364–1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00–17.5] vs. 18.5 days [3.00–53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05–2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
COVID-19 (malaltia)
SARS-CoV-2
Metilprednisolona
Tacrolimus
Inflamació
Lesió pulmonar
COVID-19
SARS-CoV-2
Metilprednisolona
Tacrolimus
Inflamación
Lesión pulmonar
COVID-19
SARS-CoV-2
Methylprednisolone
Tacrolimus
Inflammation
Lung injury
Pages
11
Publisher
Frontiers Media
Collection
8;
Is part of
Frontiers in Medicine
Citation
Solanich, Xavier; Antolí, Arnau; Rocamora-Blanch, Gemma [et al.]. Methylprednisolone pulses plus tacrolimus in addition to standard of care vs. standard of care alone in patients with severe COVID-19. A randomized controlled trial. Frontiers in Medicine, 8, 691712. Disponible en: <https://www.frontiersin.org/articles/10.3389/fmed.2021.691712/full>. Fecha de acceso: 20 jul 2021. DOI: 10.3389/fmed.2021.691712
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
© 2021 Solanich, Antolí, Rocamora-Blanch, Padullés, Fanlo-Maresma, Iriarte, Mitjavila, Capdevila, Riera-Mestre, Bas, Vicens-Zygmunt, Niubó, Calvo, Bolivar, Rigo-Bonnin, Mensa-Vilaró, Arregui, Tebe, Videla, Hereu and Corbella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/