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.
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.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Hospital Universitario Madrid Sanchinarro
Madrid, Spain