Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19

Phase 3

Completed

• Conditions: Sars-CoV-2 Infection
• Interventions: Drug: Saline solution; Drug: Evolocumab

• Registration Number: NCT04941105
• Lead Sponsor: Collegium Medicum w Bydgoszczy

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-01
• Study First Submitted: 2021-06-21
• Study First Submitted QC: 2021-06-24
• Study First Posted: 2021-06-28
• Primary Completion: 2022-05-17
• Study Completion: 2022-05-17
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-20
• Last Update Posted: 2023-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Usual Care	Saline solution	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.
PCSK9 inhibitor (evolocumab)	Evolocumab	140 mg of evolocumab as a single subcutaneous injection and standard of care accordance to the latest recommendations

Primary Outcome Measures

Name	Time	Method
Death from any cause or need for intubation	during hospitalization, up to 30 days	Indication for intubation determined individually for each patient and clinical status

Secondary Outcome Measures

Name	Time	Method
Days of intubation	during hospitalization, up to 30 days	Defined as the number of days between intubation and extubation
Change in serum interleukin-6 concentration from day 0 to day 7 and day 30	7 and 30 days from randomization
Duration of hospital stay	during hospitalization, up to 30 days	Defined as the number of days that pass between the day of hospital admission and discharge or death.
Time with Non-invasive mechanical ventilation (NIV) or High-flow nasal cannula (HFNC)	during hospitalization, up to 30 days	Defined as the number of days between initiation and cessation of Non-invasive mechanical ventilation (NIV) or High-flow nasal cannula (HFNC)
Death from any cause	during hospitalization, up to 30 days	Death from any cause during hospitalization.
Need for intubation	during hospitalization, up to 30 days	Indication for intubation determined individually for each patient and clinical status
Duration of oxygen therapy	during hospitalization, up to 30 days	Defined as the number of days of oxygen therapy (including all methods of oxygen therapy)

Trial Locations

Locations (1)

Antoni Jurasz University Hospital No. 1; 🇵🇱 Bydgoszcz, Poland