Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 (IMPACT-SIRIO 5)

Collegium Medicum w Bydgoszczy

Status and phase: Completed; Phase 3

Conditions: Sars-CoV-2 Infection

Treatments: Drug: Saline solution; Drug: Evolocumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04941105

IMPACT-SIRIO 5

Details and patient eligibility

About

The IMPACT-SIRIO 5 is a randomized, double-blind, phase III clinical trial aimed to evaluate safety and efficacy of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the COVID-19. During the hospitalization participants will be randomized in a 1:1 ratio to either receive PCSK9 inhibitor (evolocumab) or to receive placebo (saline solution). Furthermore, all people included in the study will be treated in accordance to the latest recommendations on the treatment of patients infected with SARS-CoV-2.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Written informed consent for participation in the study
2. Male and female age 18 or more at the time of signing the informed consent
3. SARS-CoV-2 infection confirmed by Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR)
4. COVID-19 pneumonia with a typical radiological changes
5. PaO2/FIO2 ratio less than or equal to 300
6. COVID-19 Pneumonia in cytokine storm with elevated serum level of interleukin-6

Exclusion criteria

1. Use of fibrates other than fenofibrate or fenofibric acid
2. Known active infections or other clinical condition that contraindicate PCSK9 inhibitors
3. Known systemic hypersensitivity to PCSK9 inhibitors
4. Estimated glomerular filtration rate <30 ml/min/1.73 m2
5. Absolute neutrophil count (ANC) less than 2000/mm3
6. A platelet count less than 50000/mm3
7. Creatine kinase (CK) greater than 3x upper limit of normal (ULN)
8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3x upper limit of normal (ULN)
9. Not expected to survive for more than 48 hours from screening
10. Unrelated co-morbidity with life expectancy <3 months.
11. Pregnancy
12. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
13. Patient being treated with other immunomodulators (except for glucocorticoids).
14. Patient included in any other interventional trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

PCSK9 inhibitor (evolocumab)

Experimental group

Description:

140 mg of evolocumab as a single subcutaneous injection and standard of care accordance to the latest recommendations

Treatment:

Drug: Evolocumab

Usual Care

Placebo Comparator group

Description:

1 ml of 0,9% saline solution as a single subcutaneous injection. Patients will be treated in accordance to the latest recommendations on caring for patients infected with SARS-CoV-2.

Treatment:

Drug: Saline solution