COVID-19Phase 3TACROVIDNCT04341038
Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
A Phase 3 study testing Tacrolimus and Methylprednisolone in people with COVID-19 and Lung Injury, run by Hospital Universitari de Bellvitge at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Lung Injury
- What is being tested?
- Tacrolimus and Methylprednisolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteSpain
- Study dates
- 1 Apr 2020to 1 Jul 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Xavier Solanich, MD, 0034 932607500 ext. 8946, xsolanich@bellvitgehospital.cat
Xavier Solanich, MD
About this study
Official title: Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19
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.
Read the 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.
- Conditions
- COVID-19, Lung Injury
- Being tested
- Tacrolimus, Methylprednisolone
- Medical subject headings
- COVID-19, Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Advagraf®, Modigraf®
the necessary dose to obtain blood levels of 8-10 ng / ml
Also called Urbason®, Solu-Moderín®
120mg of methylprednisolone daily for 3 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tacrolimus; Drug: Methylprednisolone |
| Usual care | No intervention | These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
Secondary outcomes (14)
Time to reach an afebrile state for 48 hours.
days
Measured: 56 days
Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300
days
Measured: 56 days
Time to reach FR ≤ 24 rpm for 48 hours
days
Measured: 56 days
Time to normalization of D-dimer (<250 ug / L)
days
Measured: 56 days
Time until PCR normalization (<5mg / L).
days
Measured: 56 days
Time until normalization of ferritin (<400ug / L)
days
Measured: 56 days
Study the impact of immunosuppressive treatment on viral load using quantitative PCR
viral load
Measured: 56 days
Time until hospital discharge
days
Measured: 56 days
Need for ventilatory support devices
days
Measured: 56 days
Duration that it is necessary to maintain ventilatory support.
days
Measured: 56 days
COVID-19 mortality
days
Measured: 56 days
all-cause mortality
days
Measured: 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
Measured: 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
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start1 Apr 2020
- Primary completion1 Jun 2020 (estimated)
- Study completion1 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari de Bellvitge
- Sponsor type
- University, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge
- Responsible party
- Principal investigator, Xavier Solanich, Hospital Universitari de Bellvitge
- Investigators
- Xavier Corbella, MD, PhD, Study director, Hospital Universitari de Bellvige
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04341038
- Sponsor's protocol ID
- TACRO-BELL-COVID
- Other IDs
- 2020-001445-39
- Acronym
- TACROVID
- Status last verified
- Apr 2020
- First submitted
- 7 Apr 2020
- Last updated
- 10 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34195214Solanich 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.
PubMed 33495742
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19
- ClinicalTrials.gov ID
- NCT04341038
- Acronym / sponsor ID
- TACROVID / TACRO-BELL-COVID
- Conditions
- COVID-19, Lung Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Hospital Universitari de BellvitgeUniversity, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 1 Jun 2020 (estimated)
- Study completion
- 1 Jul 2020 (estimated)
- First posted
- 10 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Tacrolimus, Drug: MethylprednisoloneMethylprednisolone 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. |
| Usual care | No intervention | –These patients can receive all the treatments considered necessary for their clinical management, except cyclosporine and tacrolimus. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Advagraf®, Modigraf®the necessary dose to obtain blood levels of 8-10 ng / ml | Drug | Intervention |
| MethylprednisoloneAlso: Urbason®, Solu-Moderín®120mg of methylprednisolone daily for 3 consecutive days | Drug | Intervention |
Primary outcome
Time to reach clinical stability
Time frame: 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
14 secondary outcomes
Time to reach an afebrile state for 48 hours.
Time frame: 56 days
Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300
Time frame: 56 days
Time to reach FR ≤ 24 rpm for 48 hours
Time frame: 56 days
Time to normalization of D-dimer (<250 ug / L)
Time frame: 56 days
Time until PCR normalization (<5mg / L).
Time frame: 56 days
Time until normalization of ferritin (<400ug / L)
Time frame: 56 days
Study the impact of immunosuppressive treatment on viral load using quantitative PCR
Time frame: 56 days
Time until hospital discharge
Time frame: 56 days
Need for ventilatory support devices
Time frame: 56 days
Duration that it is necessary to maintain ventilatory support.
Time frame: 56 days
COVID-19 mortality
Time frame: 56 days
all-cause mortality
Time frame: 56 days
Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission
Time frame: 56 days
Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone.
Time frame: 56 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Derived from this study: PubMed 34195214Solanich 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.
- Derived from this study: PubMed 33495742Solanich 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Corbella, MD, PhD study director
Hospital Universitari de Bellvige
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus and Methylprednisolone in people with COVID-19 and Lung Injury, run by Hospital Universitari de Bellvitge at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xavier Solanich, MD (0034 932607500 ext. 8946, xsolanich@bellvitgehospital.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to reach clinical stability (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04341038, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2020.