Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 4;13(17):5242.
doi: 10.3390/jcm13175242.

Cyclosporin A as an Add-On Therapy to a Corticosteroid-Based Background Treatment in Patients with COVID-19: A Multicenter, Randomized Clinical Trial

Lucía Llanos Jiménez  1 , Beatriz Alvarez-Alvarez  1 , Eva Fonseca Aizpuru  2 , Germán Peces-Barba  1 , Gloria Pindao Quesada  3 , Mª Jesús Rodríguez Nieto  1   3 , Francisco J Ruiz-Hornillos  4   5 , Luis Seijo Maceiras  6 , Ignacio Robles Barrena  7 , Alvaro Mena-de-Cea  8 , Héctor Meijide-Míguez  9 , Olga Sánchez-Pernaute  1 ; CSACOVID-IISFJD Team
Affiliations

Cyclosporin A as an Add-On Therapy to a Corticosteroid-Based Background Treatment in Patients with COVID-19: A Multicenter, Randomized Clinical Trial

Lucía Llanos Jiménez et al. J Clin Med. .

Abstract

Background: In susceptible hosts, SARS-CoV2-induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as an add-on therapy to the standard of care (SoC) in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to eight Spanish tertiary hospitals. Patients were stratified into two severity categories and randomized in a 1:1 ratio to receive a corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by Day 12 without relapses. Results: 109 patients were included and randomized, and 98 of them considered for the mITT population (51 assigned to the CsA + SoC group and 47 to the SoC group). A total of 35 (68.6%) patients from the CsA + SoC group and 32 (71.1%) patients from the SoC group reached the primary endpoint in the mITT analysis. No differences were found after stratification into age groups, in the severity level at admission, or in a combination of both. Overall, the time to FiO2 normalization was 7.4 days vs. 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: The addition of CsA did not show differences over a corticosteroid-based treatment in the clinical course of the included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Keywords: COVID-19 pneumonia; cyclosporin A; hyperinflammation; randomized controlled trial.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study participant flow diagram.
Figure 2
Figure 2
Comparison of the FiO2 requirements during hospitalization between groups. (A) Survival curves showing the probability of reaching FiO2 21% over time yielded no differences between the arms (log-rank test, p 0.48). (B) Daily FiO2 requirements in the ward-admitted patients (mean ± CI 95%).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8:420–422. doi: 10.1016/S2213-2600(20)30076-X. - DOI - PMC - PubMed
    1. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin. Infect. Dis. 2020;71:762–768. doi: 10.1093/cid/ciaa248. - DOI - PMC - PubMed
    1. Kim P.S., Read S.W., Fauci A.S. Therapy for Early COVID-19: A Critical Need. JAMA. 2020;324:2149–2150. doi: 10.1001/jama.2020.22813. - DOI - PubMed
    1. Merad M., Martin J.C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol. 2020;20:355–362. doi: 10.1038/s41577-020-0331-4. - DOI - PMC - PubMed
    1. Sanchez-Pernaute O., Romero-Bueno F.I., Selva-O A. Why choose cyclosporin A as first-line therapy in COVID-19 pneumonia. Reumatol. Clin. (Engl. Ed.) 2021;17:556–557. doi: 10.1016/j.reumae.2020.03.005. - DOI - PMC - PubMed

LinkOut - more resources