Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury

COVID-19 Clinical Trial

— TACROVID  

Official title:

Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04341038
• Other study ID #: TACRO-BELL-COVID
• Secondary ID: 2020-001445-39
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2020
• Est. completion date: July 1, 2020

Study information

• Verified date: April 2020
• Source: Hospital Universitari de Bellvitge
• Contact: Xavier Solanich, MD
• Phone: 0034 932607500
• Email: xsolanich[@]bellvitgehospital.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: July 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Lung Injury
• Wounds and Injuries

Intervention

Drug:
• Tacrolimus
the necessary dose to obtain blood levels of 8-10 ng / ml
• Methylprednisolone
120mg of methylprednisolone daily for 3 consecutive days

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitari de Bellvitge	Institut d'Investigació Biomèdica de Bellvitge

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Time to reach an afebrile state for 48 hours.	days	56 days
Secondary	Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300	days	56 days
Secondary	Time to reach FR = 24 rpm for 48 hours	days	56 days
Secondary	Time to normalization of D-dimer (<250 ug / L)	days	56 days
Secondary	Time until PCR normalization (<5mg / L).	days	56 days
Secondary	Time until normalization of ferritin (<400ug / L)	days	56 days
Secondary	Study the impact of immunosuppressive treatment on viral load using quantitative PCR	viral load	56 days
Secondary	Time until hospital discharge	days	56 days
Secondary	Need for ventilatory support devices	days	56 days
Secondary	Duration that it is necessary to maintain ventilatory support.	days	56 days
Secondary	COVID-19 mortality	days	56 days
Secondary	all-cause mortality	days	56 days
Secondary	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
Secondary	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