Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
- Registration Number
- NCT04341038
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 84
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Tacrolimus 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. Intervention Methylprednisolone 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method COVID-19 mortality 56 days days
all-cause mortality 56 days days
Need for ventilatory support devices 56 days days
Study the impact of immunosuppressive treatment on viral load using quantitative PCR 56 days viral load
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
Time until hospital discharge 56 days days
Duration that it is necessary to maintain ventilatory support. 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
Trial Locations
- Locations (1)
Hospital Universitari de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain