Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury

NCT ID: NCT04341038

Last Updated: 2020-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-01

Study Completion Date

2020-07-01

Brief Summary

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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

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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.

Conditions

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COVID-19 Lung Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The statistician who will finally carry out the analyses will be blind to the treatment received by the patients

Study Groups

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Intervention

Methylprednisolone pulses 120mg/day for 3 consecutive days (if they were not previously administered) with Tacrolimus at the necessary dose to achieve plasma levels of 8-10 ng/ml.

In addition, these patients can receive all the treatments considered necessary for their clinical management.

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type DRUG

the necessary dose to obtain blood levels of 8-10 ng / ml

Methylprednisolone

Intervention Type DRUG

120mg of methylprednisolone daily for 3 consecutive days

Usual care

These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Tacrolimus

the necessary dose to obtain blood levels of 8-10 ng / ml

Intervention Type DRUG

Methylprednisolone

120mg of methylprednisolone daily for 3 consecutive days

Intervention Type DRUG

Other Intervention Names

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Advagraf®, Modigraf® Urbason®, Solu-Moderín®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut d'Investigació Biomèdica de Bellvitge

OTHER

Sponsor Role collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role lead

Responsible Party

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Xavier Solanich

Xavier Solanich, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xavier Corbella, MD, PhD

Role: STUDY_DIRECTOR

Hospital Universitari de Bellvige

Locations

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Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Xavier Solanich, MD

Role: CONTACT

0034 932607500 ext. 8946

Facility Contacts

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Xavier Solanich, MD

Role: primary

0034 932607500 ext. 8946

References

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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.

Reference Type DERIVED
PMID: 34195214 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33495742 (View on PubMed)

Other Identifiers

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2020-001445-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TACRO-BELL-COVID

Identifier Type: -

Identifier Source: org_study_id

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