COVID-19, Lung Injury
Conditions
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.
Interventions
DRUGTacrolimus
the necessary dose to obtain blood levels of 8-10 ng / ml
DRUGMethylprednisolone
120mg of methylprednisolone daily for 3 consecutive days
Sponsors
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 to reach an afebrile state for 48 hours. | 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 |
| Time until hospital discharge | 56 days | days |
Countries
Spain
Contacts
Primary ContactXavier Solanich, MD
Outcome results
None listed