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

Sponsor

Hospital Universitari de Bellvitge (Other)

Overall Status

Unknown status

CT.gov ID

NCT04341038

Collaborator

Institut d'Investigació Biomèdica de Bellvitge (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

28.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Lung Injury	Drug: Tacrolimus Drug: Methylprednisolone	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

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

Primary Purpose:

Treatment

Official Title:

Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19

Actual Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Jun 1, 2020

Anticipated Study Completion Date :

Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tacrolimus the necessary dose to obtain blood levels of 8-10 ng / ml Other Names: Advagraf®, Modigraf® Drug: Methylprednisolone 120mg of methylprednisolone daily for 3 consecutive days Other Names: Urbason®, Solu-Moderín®
No Intervention: Usual care These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Tacrolimus

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

Other Names:

Advagraf®, Modigraf®

Drug: Methylprednisolone

120mg of methylprednisolone daily for 3 consecutive days

Other Names:

Urbason®, Solu-Moderín®

No Intervention: Usual care

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

Outcome Measures

Primary Outcome Measures

Time to reach clinical stability [28 days]
Assess the days until clinical stability is achieved after initiating randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury. Clinical stability is defined if all the following criteria are met for 48 consecutive hours: Body temperature ≤ 37.0ºC; PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300; Respiratory rate ≤ 24 rpm

Secondary Outcome Measures

Time to reach an afebrile state for 48 hours. [56 days]
days
Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300 [56 days]
days
Time to reach FR ≤ 24 rpm for 48 hours [56 days]
days
Time to normalization of D-dimer (<250 ug / L) [56 days]
days
Time until PCR normalization (<5mg / L). [56 days]
days
Time until normalization of ferritin (<400ug / L) [56 days]
days
Study the impact of immunosuppressive treatment on viral load using quantitative PCR [56 days]
viral load
Time until hospital discharge [56 days]
days
Need for ventilatory support devices [56 days]
days
Duration that it is necessary to maintain ventilatory support. [56 days]
days
COVID-19 mortality [56 days]
days
all-cause mortality [56 days]
days
Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission [56 days]
cytokines quantification technique by Luminex
Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone. [56 days]
IDIBELL Clinical Research and Clinical Trials Unit will oversee the monitoring and pharmacovigilance

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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