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

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ClinicalTrials.gov Identifier: NCT04341038
Recruitment Status : Recruiting
First Posted : April 10, 2020
Last Update Posted : April 10, 2020
Sponsor:
Collaborator:
Institut d'Investigació Biomèdica de Bellvitge
Information provided by (Responsible Party):
Xavier Solanich, Hospital Universitari de Bellvitge

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 1, 2020
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : July 1, 2020


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 Name: Advagraf®, Modigraf®

Drug: Methylprednisolone
120mg of methylprednisolone daily for 3 consecutive days
Other Name: Urbason®, Solu-Moderín®

No Intervention: Usual care
These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus.



Primary Outcome Measures :
  1. Time to reach clinical stability [ Time Frame: 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 :
  1. Time to reach an afebrile state for 48 hours. [ Time Frame: 56 days ]
    days

  2. Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300 [ Time Frame: 56 days ]
    days

  3. Time to reach FR ≤ 24 rpm for 48 hours [ Time Frame: 56 days ]
    days

  4. Time to normalization of D-dimer (<250 ug / L) [ Time Frame: 56 days ]
    days

  5. Time until PCR normalization (<5mg / L). [ Time Frame: 56 days ]
    days

  6. Time until normalization of ferritin (<400ug / L) [ Time Frame: 56 days ]
    days

  7. Study the impact of immunosuppressive treatment on viral load using quantitative PCR [ Time Frame: 56 days ]
    viral load

  8. Time until hospital discharge [ Time Frame: 56 days ]
    days

  9. Need for ventilatory support devices [ Time Frame: 56 days ]
    days

  10. Duration that it is necessary to maintain ventilatory support. [ Time Frame: 56 days ]
    days

  11. COVID-19 mortality [ Time Frame: 56 days ]
    days

  12. all-cause mortality [ Time Frame: 56 days ]
    days

  13. Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission [ Time Frame: 56 days ]
    cytokines quantification technique by Luminex

  14. Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone. [ Time Frame: 56 days ]
    IDIBELL Clinical Research and Clinical Trials Unit will oversee the monitoring and pharmacovigilance



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04341038


Contacts
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Contact: Xavier Solanich, MD 0034 932607500 ext 8946 xsolanich@bellvitgehospital.cat

Locations
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Spain
Hospital Universitari de Bellvitge Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: Xavier Solanich, MD    0034 932607500 ext 8946    xsolanich@bellvitgehospital.cat   
Principal Investigator: Xavier Solanich, MD         
Sub-Investigator: Arnau Antolí, MD         
Sponsors and Collaborators
Hospital Universitari de Bellvitge
Institut d'Investigació Biomèdica de Bellvitge
Investigators
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Study Director: Xavier Corbella, MD, PhD Hospital Universitari de Bellvige
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Responsible Party: Xavier Solanich, Xavier Solanich, MD, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT04341038    
Other Study ID Numbers: TACRO-BELL-COVID
2020-001445-39 ( EudraCT Number )
First Posted: April 10, 2020    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lung Injury
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Tacrolimus
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal