Ruxo-Sim-20: Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.
Study Details
Study Description
Brief 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. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ruxolitinib plus simvastatin 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. |
Drug: Ruxolitinib plus simvastatin
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
|
| Other: Standard of Care Patients will receive treatment according to usual clinical practice in the participant site. |
Other: Standard of Care
Patients will receive treatment according to usual clinical practice in the participant site.
|
Outcome Measures
Primary Outcome Measures
- Percentage of patients who develop severe respiratory failure. [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.
Secondary Outcome Measures
- Percentage of patients who develop severe respiratory failure. [14 days]
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 14 from randomization.
- Length of ICU stay. [28 days]
Time from ICU admision to ICU discharge.
- Length of hospital stay [28 days]
Time from hospital admision to hospital discharge.
- Survival rate at 6 months [6 months]
Percentage of patients alive at 6 months
- Survival rate at 12 months [12 months]
Percentage of patients alive at 12 months
- Survival rate at 28 days [28 days]
Percentage of patients who died from any cause 28 days after inclusion in the study
- Percentage of patients with each AE by grade [28 days]
Percentage of patients with each AE by grade in relation with total number of treated patients
- Percentage of patients who discontinued due to AEs [28 days]
Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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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.
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Platelets> 50,000 / uL, neutrophils> 500 / ul
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Kidney or liver failure is not a contraindication, dose adjustment will be made according to the SmPC
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Women of childbearing potential who are sexually active, not undergoing a hysterectomy or double adnexectomy, should follow the following indications for contraception:
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Negative serum or urine pregnancy test in the 72 hours prior to the start of treatment.
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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.
Exclusion Criteria:
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Documented concomitant severe bacterial or fungal infection
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Infection with HIV, HCV, HBV
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Age <18 years
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Thrombocytopenia <50,000 / uL, Neutropenia <500 / uL
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Women of childbearing age who do not use an effective contraceptive method.
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Pregnant or lactating women.
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Patients who do not want or cannot comply with the protocol.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario Madrid Sanchinarro | Madrid | Spain | 28050 |
Sponsors and Collaborators
- Fundación de investigación HM
- Apices Soluciones S.L.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Ruxo-Sim-20
- 2020-001405-23