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

Solanich, Xavier; Antolí, Arnau; Padullés, N; Fanlo-Maresma, Marta; Iriarte, Adriana; Mitjavila, Francesca; Capdevila, Orestes González; Molina-Molina, María; Sabater, J.; Bas, Jordi; Mensa‐Vilaró, Anna; Niubó, Jordi; Calvo, Naiara; Bolivar, Santiago; Rigo-Bonnin, Raül; Arregui, Laura; Tebé, Cristian; Hereu, Pilar; Videla, Sebastián; Corbella, Xavier

doi:10.1016/j.conctc.2021.100716

Cited by 18 publications

(16 citation statements)

References 30 publications

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“…A TACROVID trial showed that methylprednisolone and tacrolimus might have a beneficial effect in COVID‐19 patients with severe pulmonary failure and systemic hyperinflammatory syndrome, probably due to the ability of tacrolimus to inhibit both the SARS‐CoV‐2 replication and the secondary cytokine storm. 47 A recently published meta‐analysis that included 202 solid organ transplant recipients concluded that receiving tacrolimus could benefit COVID‐19. However, their study included only 125 renal transplant recipients and was based generally on case reports or case series.…”

Section: Discussionmentioning

confidence: 99%

Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

Jukić

Jurić

Furić-Čunko

et al. 2021

Immunity Inflam & Disease

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Introduction Although most patients recover within several weeks after acute COVID‐19, some of them develop long‐lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID‐19. We aimed to describe complications occurring after COVID‐19 in this group of patients. Methods A prospective single‐center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase‐polymerase chain reaction (RT‐PCR) tests for SARS‐CoV‐2 after COVID‐19 were eligible for further follow‐up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID‐19. Results Only 11.53% of renal transplant recipients who survived acute COVID‐19 were symptomless and free from new‐onset laboratory abnormalities during the median follow‐up of 64 days (range: 50–76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self‐reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D‐dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT‐PCR for cytomegalovirus (8.7%), Epstein–Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD‐EPI as predictors for the development of post‐COVID clinical complications. Six months after acute COVID‐19, elevated D‐dimers persisted with normalization of other laboratory parameters. Twenty‐nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients. Conclusion Post‐COVID‐19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID‐19 should undergo long‐term monitoring for evaluation and treatment of complications.

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Section: Discussionmentioning

confidence: 99%

Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

Jukić

Jurić

Furić-Čunko

et al. 2021

Immunity Inflam & Disease

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“…However, gender-based statistical analysis was not performed, and some female-related pharmacokinetics differences in cyclosporine or tacrolimus concentrations might have been diluted within the large number of males (71.2%) enrolled in the study [106] , [107] . Based on the beneficial effects of cyclosporine, tacrolimus, and everolimus in Covid-19 transplanted patients, the pragmatical, randomized (1:1), open-label, single-center, phase II TACROVID clinical trial has been designed to evaluate the efficacy and safety of methylprednisolone pulses, tacrolimus, and standard of care in severe COVID-19 patients [108] . TACROVID is still recruiting (NCT04341038), and patients are randomly assigned 1:1 to the experimental arm receiving methylprednisolone pulses of 120 mg/day for three consecutive days and tacrolimus twice daily to achieve a trough concentration of 8-10 ng/mL.…”

Section: Immunosuppressive and Immunomodulatory Drugsmentioning

confidence: 99%

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity

Spini

Giudice

Brancaleone

et al. 2021

Pharmacological Research

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Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomised clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3,000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.

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“…Therefore, we agree that the use of CsA might be justified in those severe COVID-19 patients at risk to transit into the second stage of the disease, by blocking the excessive inflammatory response, but not at the early stages, when viral growth and spread occurs. In this regard, we have recently launched a randomized controlled trial (RCT) using tacrolimus to treat severe COVID-19 patients, 6 and we encourage the development of new other RCTs to assess the efficacy and safety of calcineurin inhibitors, at recommended dose, focused on to tackle the systemic host-immune hyperinflammatory response present in severe COVID-19.…”

mentioning

confidence: 99%

Inhibition of SARS‐CoV‐2 replication using calcineurin inhibitors: are concentrations required clinically achievable?

et al. 2021

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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

Cited by 18 publications

References 30 publications

Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity

Inhibition of SARS‐CoV‐2 replication using calcineurin inhibitors: are concentrations required clinically achievable?

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