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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

Tracking Information
First Submitted Date  ICMJE April 7, 2020
First Posted Date  ICMJE April 10, 2020
Last Update Posted Date April 10, 2020
Actual Study Start Date  ICMJE April 1, 2020
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2020)
  • Time to reach an afebrile state for 48 hours. [ Time Frame: 56 days ]
    days
  • Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300 [ Time Frame: 56 days ]
    days
  • Time to reach FR ≤ 24 rpm for 48 hours [ Time Frame: 56 days ]
    days
  • Time to normalization of D-dimer (<250 ug / L) [ Time Frame: 56 days ]
    days
  • Time until PCR normalization (<5mg / L). [ Time Frame: 56 days ]
    days
  • Time until normalization of ferritin (<400ug / L) [ Time Frame: 56 days ]
    days
  • Study the impact of immunosuppressive treatment on viral load using quantitative PCR [ Time Frame: 56 days ]
    viral load
  • Time until hospital discharge [ Time Frame: 56 days ]
    days
  • Need for ventilatory support devices [ Time Frame: 56 days ]
    days
  • Duration that it is necessary to maintain ventilatory support. [ Time Frame: 56 days ]
    days
  • COVID-19 mortality [ Time Frame: 56 days ]
    days
  • all-cause mortality [ Time Frame: 56 days ]
    days
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
Official Title  ICMJE Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • COVID-19
  • Lung Injury
Intervention  ICMJE
  • 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®
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Tacrolimus
    • Drug: Methylprednisolone
  • No Intervention: Usual care
    These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus.
Publications * Solanich X, Antolí A, Padullés N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Molina M, Sabater J, Bas J, Mensa-Vilaró A, Niubó J, Calvo N, Bolivar S, Rigo-Bonnin R, Arregui L, Tebé 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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 8, 2020)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2020
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xavier Solanich, MD 0034 932607500 ext 8946 xsolanich@bellvitgehospital.cat
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04341038
Other Study ID Numbers  ICMJE TACRO-BELL-COVID
2020-001445-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xavier Solanich, Hospital Universitari de Bellvitge
Study Sponsor  ICMJE Hospital Universitari de Bellvitge
Collaborators  ICMJE Institut d'Investigació Biomèdica de Bellvitge
Investigators  ICMJE
Study Director: Xavier Corbella, MD, PhD Hospital Universitari de Bellvige
PRS Account Hospital Universitari de Bellvitge
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP