Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.

NCT04348695 | Completed Phase 2

• 2 other identifiers: Ruxo-Sim-202020-001405-23
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronavirus Infection

Keywords

COVID19; simvastatin; ruxolitinib

Outcome Measures

Primary Outcomes (1)

• 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.

  7 days

Secondary Outcomes (8)

• Percentage of patients who develop severe respiratory failure.

  14 days

• Length of ICU stay.

  28 days

• Length of hospital stay

  28 days

• Survival rate at 6 months

  6 months

• Survival rate at 12 months

  12 months

Study Arms (2)

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.

Drug: Ruxolitinib plus simvastatin

Standard of Care

OTHER

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

Other: Standard of Care

Interventions

Ruxolitinib plus simvastatin DRUG

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

Ruxolitinib plus simvastatin

Standard of Care OTHER

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

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación de investigación HM: lead
• Apices Soluciones S.L.: collaborator

Study Sites (1)

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Related Publications (2)

• 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.

  PMID: 37143685 DERIVED

• Sultana 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.

  PMID: 33240091 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

ruxolitinib; Simvastatin; Standard of Care

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 16, 2020
• Study Start: April 12, 2020
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: June 6, 2022

Record last verified: 2022-06

Locations

ES (1)