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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001445-39 | EudraCT Number |
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| Name | Class |
|---|---|
| Institut d'Investigació Biomèdica de Bellvitge | OTHER |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | 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. |
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| Usual care | No Intervention | These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus | Drug | the necessary dose to obtain blood levels of 8-10 ng / ml |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach clinical stability | 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 | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach an afebrile state for 48 hours. | days | 56 days |
| Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300 | days | 56 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xavier Solanich, MD | Contact | 0034 932607500 | 8946 | xsolanich@bellvitgehospital.cat |
| Name | Affiliation | Role |
|---|---|---|
| Xavier Corbella, MD, PhD | Hospital Universitari de Bellvige | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitari de Bellvitge | Recruiting | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34195214 | Derived | Solanich X, Antoli A, Rocamora-Blanch G, Padulles N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Riera-Mestre A, Bas J, Vicens-Zygmunt V, Niubo J, Calvo N, Bolivar S, Rigo-Bonnin R, Mensa-Vilaro A, Arregui L, Tebe C, Videla S, Hereu P, Corbella X. Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial. Front Med (Lausanne). 2021 Jun 14;8:691712. doi: 10.3389/fmed.2021.691712. eCollection 2021. | |
| 33495742 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D055370 | Lung Injury |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011239 | Prednisolone |
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The statistician who will finally carry out the analyses will be blind to the treatment received by the patients
| Methylprednisolone | Drug | 120mg of methylprednisolone daily for 3 consecutive days |
|
|
| Time to reach FR ≤ 24 rpm for 48 hours | days | 56 days |
| Time to normalization of D-dimer (<250 ug / L) | days | 56 days |
| Time until PCR normalization (<5mg / L). | days | 56 days |
| Time until normalization of ferritin (<400ug / L) | days | 56 days |
| Study the impact of immunosuppressive treatment on viral load using quantitative PCR | viral load | 56 days |
| Time until hospital discharge | days | 56 days |
| Need for ventilatory support devices | days | 56 days |
| Duration that it is necessary to maintain ventilatory support. | days | 56 days |
| COVID-19 mortality | days | 56 days |
| all-cause mortality | days | 56 days |
| Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission | cytokines quantification technique by Luminex | 56 days |
| Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone. | IDIBELL Clinical Research and Clinical Trials Unit will oversee the monitoring and pharmacovigilance | 56 days |
| Derived |
| Solanich X, Antoli A, Padulles N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Molina M, Sabater J, Bas J, Mensa-Vilaro A, Niubo J, Calvo N, Bolivar S, Rigo-Bonnin R, Arregui L, Tebe 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. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D013898 | Thoracic Injuries |
| D014947 | Wounds and Injuries |
| D011246 |
| Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |