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

Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19: the Randomized, Double-blind, Phase III IMPACT-SIRIO 5 Study.

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.

Study Overview

• Status: Completed
• Conditions: Sars-CoV-2 Infection
• Intervention / Treatment: Drug: Evolocumab; Drug: Saline solution

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland
    • Antoni Jurasz University Hospital No. 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCSK9 inhibitor (evolocumab); 140 mg of evolocumab as a single subcutaneous injection and standard of care accordance to the latest recommendations	Drug: Evolocumab; A single subcutaneous administration of 140 mg evolocumab
Placebo Comparator: Usual Care; 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.	Drug: Saline solution; A single subcutaneous injection of 1ml of 0,9% saline solution

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Jacek Kubica, MD, PhD, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; Principal Investigator: Eliano Navarese, Md, PhD, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; PCSK9 inhibitor; SARS-CoV-2 Pneumonia
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: IMPACT-SIRIO 5

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No