Clinical trial NCT04348695: Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Infection
Keywords: COVID19
simvastatin
ruxolitinib
Lead sponsor: Fundación de investigación HM
Sponsor class: OTHER
Collaborators: name: Apices Soluciones S.L.
First posted: 2020-04-16
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of patients who develop severe respiratory failure.
timeFrame: 7 days
Secondary outcomes:
measure: Percentage of patients who develop severe respiratory failure.
timeFrame: 14 days
measure: Length of ICU stay.
timeFrame: 28 days
measure: Length of hospital stay
timeFrame: 28 days
measure: Survival rate at 6 months
timeFrame: 6 months
measure: Survival rate at 12 months
timeFrame: 12 months
measure: Survival rate at 28 days
timeFrame: 28 days
measure: Percentage of patients with each AE by grade
timeFrame: 28 days
measure: Percentage of patients who discontinued due to AEs
timeFrame: 28 days
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
Study officials:
References:
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.