Back to resultsStudy of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19. (Ruxo-Sim-20)
Primary Purpose
Coronavirus Infection
Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Ruxolitinib plus simvastatin
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus Infection focused on measuring COVID19, simvastatin, ruxolitinib
Eligibility Criteria
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
Sites / Locations
- Hospital Universitario Madrid Sanchinarro
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Ruxolitinib plus simvastatin
Standard of Care
Arm 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.
Patients will receive treatment according to usual clinical practice in the participant site.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Length of ICU stay.
Time from ICU admision to ICU discharge.
Length of hospital stay
Time from hospital admision to hospital discharge.
Survival rate at 6 months
Percentage of patients alive at 6 months
Survival rate at 12 months
Percentage of patients alive at 12 months
Survival rate at 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
Percentage of patients with each AE by grade in relation with total number of treated patients
Percentage of patients who discontinued due to AEs
Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Full Information
NCT ID
NCT04348695
First Posted
April 13, 2020
Last Updated
June 3, 2022
Sponsor
Fundación de investigación HM
Collaborators
Apices Soluciones S.L.
1. Study Identification
Unique Protocol Identification Number
NCT04348695
Brief Title
Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.
Acronym
Ruxo-Sim-20
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.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
April 12, 2020 (Actual)
Primary Completion Date
January 31, 2021 (Actual)
Study Completion Date
January 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación de investigación HM
Collaborators
Apices Soluciones S.L.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infection
Keywords
COVID19, simvastatin, ruxolitinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib plus simvastatin
Arm Type
Experimental
Arm 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.
Arm Title
Standard of Care
Arm Type
Other
Arm Description
Patients will receive treatment according to usual clinical practice in the participant site.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib plus simvastatin
Intervention 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
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Patients will receive treatment according to usual clinical practice in the participant site.
Primary Outcome Measure Information:
Title
Percentage of patients who develop severe respiratory failure.
Description
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Percentage of patients who develop severe respiratory failure.
Description
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 14 from randomization.
Time Frame
14 days
Title
Length of ICU stay.
Description
Time from ICU admision to ICU discharge.
Time Frame
28 days
Title
Length of hospital stay
Description
Time from hospital admision to hospital discharge.
Time Frame
28 days
Title
Survival rate at 6 months
Description
Percentage of patients alive at 6 months
Time Frame
6 months
Title
Survival rate at 12 months
Description
Percentage of patients alive at 12 months
Time Frame
12 months
Title
Survival rate at 28 days
Description
Percentage of patients who died from any cause 28 days after inclusion in the study
Time Frame
28 days
Title
Percentage of patients with each AE by grade
Description
Percentage of patients with each AE by grade in relation with total number of treated patients
Time Frame
28 days
Title
Percentage of patients who discontinued due to AEs
Description
Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Hospital Universitario Madrid Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33240091
Citation
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.
Results Reference
derived
Learn more about this trial
Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.
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