Clinical trial NCT04341038: Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
Official title: Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Lung Injury
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Institut d'Investigació Biomèdica de Bellvitge
First posted: 2020-04-10
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the days until reaching clinical stability after starting randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury.

Detailed description: Unfortunately, the treatment of COVID-19 disease is still based on life support therapies. Nowadays, there is no scientific evidence from clinical trials regarding the efficacy or safety of different drugs to treat COVID-19 patients, despite some of them evolving to fatal severe lung injury due to important inflammatory process secondary to pro-inflammatory cytokines. Interestingly, Tacrolimus has been shown to inhibit both pro-inflammatory cytokines and, also, human coronavirus SARS-Cov replication, but it has not specifically been tested in COVID-19 patients.

Our working hypothesis is that severe SARS-CoV-2 (COVID-19) pneumonia is secondary to a deleterious inflammatory process; so, the use of Methylprednisolone pulses and Tacrolimus in hospitalized severe COVID-19 lung injury patients might have a positive clinical effect.

Given the COVID-19 current health emergency, this study could provide useful evidence to treat some COVID-19 patients with Methylprednisolona and Tacrolimus, which might represent a new therapeutic option for them. Tacrolimus is a drug with more than 20 years of experience, and therefore, its side effects are well known and usually reversible. In addition, since tacrolimus is a low-cost and easy to produce at large-scale drug, it could be used to treat a large number of patients. The administration of this drugs could not only decrease mortality secondary to lung involvement by COVID-19, but also decrease the excessive burden of care that intensive care units are bearing.

Eligibility criteria: Inclusion Criteria:

* COVID-19 infection confirmed by PCR
* New onset radiological infiltrates
* Respiratory failure (PaO2 / FiO2 \<300 or satO2 / FiO2 \<220)
* PCR\>100 mg/L and/or D-Dimer\>1000 µg/L and/or Ferritin\>1000 ug/L
* Informed consent.

Exclusion Criteria:

* Life expectancy ≤ 24h
* Glomerular filtration ≤ 30 ml / min / 1.73 m2
* Leukopenia ≤ 4000 cells / µL
* Concomitant potentially serious infections.
* Contraindication for the use of tacrolimus according to the specifications of the product
* Known adverse reactions to treatment
* Have participated in a clinical trial in the last 3 months

Primary outcomes:
measure: Time to reach clinical stability
timeFrame: 28 days
Secondary outcomes:
measure: Time to reach an afebrile state for 48 hours.
timeFrame: 56 days
measure: Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300
timeFrame: 56 days
measure: Time to reach FR ≤ 24 rpm for 48 hours
timeFrame: 56 days
measure: Time to normalization of D-dimer (<250 ug / L)
timeFrame: 56 days
measure: Time until PCR normalization (<5mg / L).
timeFrame: 56 days
measure: Time until normalization of ferritin (<400ug / L)
timeFrame: 56 days
measure: Study the impact of immunosuppressive treatment on viral load using quantitative PCR
timeFrame: 56 days
measure: Time until hospital discharge
timeFrame: 56 days
measure: Need for ventilatory support devices
timeFrame: 56 days
measure: Duration that it is necessary to maintain ventilatory support.
timeFrame: 56 days
measure: COVID-19 mortality
timeFrame: 56 days
measure: all-cause mortality
timeFrame: 56 days
measure: Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission
timeFrame: 56 days
measure: Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone.
timeFrame: 56 days
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
Study officials:
affiliation: Hospital Universitari de Bellvige
name: Xavier Corbella, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Solanich X, Antoli A, Rocamora-Blanch G, Padulles N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Riera-Mestre A, Bas J, Vicens-Zygmunt V, Niubo J, Calvo N, Bolivar S, Rigo-Bonnin R, Mensa-Vilaro A, Arregui L, Tebe C, Videla S, Hereu P, Corbella X. 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. Front Med (Lausanne). 2021 Jun 14;8:691712. doi: 10.3389/fmed.2021.691712. eCollection 2021.
citation: Solanich X, Antoli A, Padulles N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Molina M, Sabater J, Bas J, Mensa-Vilaro A, Niubo J, Calvo N, Bolivar S, Rigo-Bonnin R, Arregui L, Tebe C, Hereu P, Videla S, Corbella X. Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: The TACROVID trial protocol. Contemp Clin Trials Commun. 2021 Mar;21:100716. doi: 10.1016/j.conctc.2021.100716. Epub 2021 Jan 19.