Coronavirus InfectionPhase 2Ruxo-Sim-20NCT04348695
Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.
A Phase 2 study testing Ruxolitinib plus simvastatin in people with Coronavirus Infection, run by Fundación de investigación HM at 1 site in Spain.
Trial summary
COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus Infection
- What is being tested?
- Ruxolitinib plus simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteSpain
- Study dates
- 12 Apr 2020to 31 Jan 2021
- Phase
- Phase 2
- 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
- Patients who have given their written informed consent. If it is considered that obtaining written consent could constitute a factor for the transmission of the disease (given the high contagiousness of the SARS-Cov-2 virus), it will be permitted to obtain duly justified verbal consent in the patient's medical history.
- Clinical diagnosis or confirmed by analytical tests (PCR of viral RNA or detection of antiSARS-Cov-2 antibodies) that requires care in hospital and that are grade 3 or 4 of the WHO 7-point ordinal scale of severity categorization for COVID.
- Platelets> 50,000 / uL, neutrophils> 500 / ul
- Kidney or liver failure is not a contraindication, dose adjustment will be made according to the SmPC
- Women of childbearing potential who are sexually active, not undergoing a hysterectomy or double adnexectomy, should follow the following indications for contraception:
- Negative serum or urine pregnancy test in the 72 hours prior to the start of treatment.
- Use of a medically accepted contraceptive method during: 2 months prior to the start of study treatment, during the study and up to 3 months after the last dose of treatment.
Who cannot join
- Documented concomitant severe bacterial or fungal infection
- Infection with HIV, HCV, HBV
- Age <18 years
- Thrombocytopenia <50,000 / uL, Neutropenia <500 / uL
- Women of childbearing age who do not use an effective contraceptive method.
- Pregnant or lactating women.
- Patients who do not want or cannot comply with the protocol.
- Patients with impaired gastrointestinal function or gastric disease that significantly impairs the absorption of ruxolitinib or simvastatin, such as: severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive resection (> 1m) of the small intestine or inability to swallow oral medication. Previous partial or total gastrectomy is not an exclusion criterion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Clinical Trial of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.Ruxo-Sim-20 Clinical Trial.
COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine.
Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response.
Read more
Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19.
Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection.
In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.
- Conditions
- Coronavirus Infection
- Being tested
- Ruxolitinib plus simvastatin, Standard of Care
- Keywords
- COVID19, simvastatin, ruxolitinib
- Medical subject headings
- Coronavirus Infections, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ruxolitinib plus simvastatinDrug
Ruxolitinib 5 mg orally every 12 hours for 7 days, which will be increased to 10 mg every 12 hours for a total of 14 days.
Simvastatin 40 mg orally every 24 hours for 14 days
Standard of CareOther
Patients will receive treatment according to usual clinical practice in the participant site.
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib plus simvastatin | Experimental | Ruxolitinib 5 mg orally every 12 hours for 7 days, which will be increased to 10 mg every 12 hours for a total of 14 days.
Simvastatin 40 mg orally every 24 hours for 14 days. Receives: Drug: Ruxolitinib plus simvastatin |
| Standard of Care | Other | Patients will receive treatment according to usual clinical practice in the participant site. Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients who develop severe respiratory failure.
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
Measured: 7 days
Secondary outcomes (8)
Percentage of patients who develop severe respiratory failure.
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 14 from randomization.
Measured: 14 days
Length of ICU stay.
Time from ICU admision to ICU discharge.
Measured: 28 days
Length of hospital stay
Time from hospital admision to hospital discharge.
Measured: 28 days
Survival rate at 6 months
Percentage of patients alive at 6 months
Measured: 6 months
Survival rate at 12 months
Percentage of patients alive at 12 months
Measured: 12 months
Survival rate at 28 days
Percentage of patients who died from any cause 28 days after inclusion in the study
Measured: 28 days
Percentage of patients with each AE by grade
Percentage of patients with each AE by grade in relation with total number of treated patients
Measured: 28 days
Percentage of patients who discontinued due to AEs
Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start12 Apr 2020
- Primary completion31 Jan 2021
- Study completion31 Jan 2021
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 Coronavirus InfectionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación de investigación HM
- Sponsor type
- University, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04348695
- Sponsor's protocol ID
- Ruxo-Sim-20
- Other IDs
- 2020-001405-23
- Acronym
- Ruxo-Sim-20
- Status last verified
- Jun 2022
- First submitted
- 13 Apr 2020
- Last updated
- 6 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Garcia-Donas J, Martinez-Urbistondo D, Velazquez Kennedy K, Villares P, Barquin A, Dominguez A, Rodriguez-Moreno JF, Caro E, Suarez Del Villar R, Nistal-Villan E, Yague M, Ortiz M, Barba M, Ruiz-Llorente S, Quiralte M, Zanin M, Rodriguez C, Navarro P, Berraondo P, Madurga R. Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution. Front Immunol. 2023 Apr 18;14:1156603. doi: 10.3389/fimmu.2023.1156603. eCollection 2023.
PubMed 37143685Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.
PubMed 33240091
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Clinical Trial of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.Ruxo-Sim-20 Clinical Trial.
- ClinicalTrials.gov ID
- NCT04348695
- Acronym / sponsor ID
- Ruxo-Sim-20 / Ruxo-Sim-20
- Conditions
- Coronavirus Infection
- Keywords
- COVID19, simvastatin, ruxolitinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Fundación de investigación HMUniversity, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Study start
- 12 Apr 2020 (actual)
- Primary completion
- 31 Jan 2021 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 16 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.
COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine.
Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response.
Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19.
Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection.
In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib plus simvastatin | Experimental | Drug: Ruxolitinib plus simvastatinRuxolitinib 5 mg orally every 12 hours for 7 days, which will be increased to 10 mg every 12 hours for a total of 14 days. Simvastatin 40 mg orally every 24 hours for 14 days. |
| Standard of Care | Other | Other: Standard of CarePatients will receive treatment according to usual clinical practice in the participant site. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients who have given their written informed consent. If it is considered that obtaining written consent could constitute a factor for the transmission of the disease (given the high contagiousness of the SARS-Cov-2 virus), it will be permitted to obtain duly justified verbal consent in the patient's medical history.
- Clinical diagnosis or confirmed by analytical tests (PCR of viral RNA or detection of antiSARS-Cov-2 antibodies) that requires care in hospital and that are grade 3 or 4 of the WHO 7-point ordinal scale of severity categorization for COVID.
- Platelets> 50,000 / uL, neutrophils> 500 / ul
- Kidney or liver failure is not a contraindication, dose adjustment will be made according to the SmPC
- Women of childbearing potential who are sexually active, not undergoing a hysterectomy or double adnexectomy, should follow the following indications for contraception:
Key exclusion criteria (8 listed)
- Documented concomitant severe bacterial or fungal infection
- Infection with HIV, HCV, HBV
- Age <18 years
- Thrombocytopenia <50,000 / uL, Neutropenia <500 / uL
- Women of childbearing age who do not use an effective contraceptive method.
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 |
|---|---|---|
| Ruxolitinib plus simvastatinRuxolitinib 5 mg orally every 12 hours for 7 days, which will be increased to 10 mg every 12 hours for a total of 14 days. Simvastatin 40 mg orally every 24 hours for 14 days | Drug | Ruxolitinib plus simvastatin |
| Standard of CarePatients will receive treatment according to usual clinical practice in the participant site. | Other | Standard of Care |
Primary outcome
Percentage of patients who develop severe respiratory failure.
Time frame: 7 days
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
8 secondary outcomes
Percentage of patients who develop severe respiratory failure.
Time frame: 14 days
Length of ICU stay.
Time frame: 28 days
Length of hospital stay
Time frame: 28 days
Survival rate at 6 months
Time frame: 6 months
Survival rate at 12 months
Time frame: 12 months
Survival rate at 28 days
Time frame: 28 days
Percentage of patients with each AE by grade
Time frame: 28 days
Percentage of patients who discontinued due to AEs
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2022.
- Derived from this study: PubMed 37143685Garcia-Donas J, Martinez-Urbistondo D, Velazquez Kennedy K, Villares P, Barquin A, Dominguez A, Rodriguez-Moreno JF, Caro E, Suarez Del Villar R, Nistal-Villan E, Yague M, Ortiz M, Barba M, Ruiz-Llorente S, Quiralte M, Zanin M, Rodriguez C, Navarro P, Berraondo P, Madurga R. Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution. Front Immunol. 2023 Apr 18;14:1156603. doi: 10.3389/fimmu.2023.1156603. eCollection 2023.
- Derived from this study: PubMed 33240091Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib plus simvastatin in people with Coronavirus Infection, run by Fundación de investigación HM 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 7 inclusion and 8 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: finished, as of the sponsor's last update on 6 Jun 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients who develop severe respiratory failure. (time frame: 7 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 NCT04348695, 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 6 Jun 2022.