Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19. (Ruxo-Sim-20)

Fundación de investigación HM

Status and phase: Completed; Phase 2

Conditions: Coronavirus Infection

Treatments: Drug: Ruxolitinib plus simvastatin; Other: Standard of Care

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04348695

Ruxo-Sim-20

2020-001405-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups

Ruxolitinib plus simvastatin

Experimental group

Description:

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.

Treatment:

Drug: Ruxolitinib plus simvastatin

Standard of Care

Other group

Description:

Patients will receive treatment according to usual clinical practice in the participant site.

Treatment:

Other: Standard of Care