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

• ClinicalTrials.gov Identifier: NCT04941105
• Recruitment Status: Completed
• First Posted: June 28, 2021
• Last Update Posted: April 21, 2023
• Sponsor: Collegium Medicum w Bydgoszczy
• Information provided by (Responsible Party): Jacek Kubica, Collegium Medicum w Bydgoszczy

Tracking Information

• First Submitted Date: June 21, 2021
• First Posted Date: June 28, 2021
• Last Update Posted Date: April 21, 2023
• Actual Study Start Date: June 1, 2021
• Actual Primary Completion Date: May 17, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2022)

Death from any cause or need for intubation [ Time Frame: during hospitalization, up to 30 days ]

Indication for intubation determined individually for each patient and clinical status

Original Primary Outcome Measures (submitted: June 24, 2021)

• Need for intubation [ Time Frame: during hospitalization, up to 30 days ]
  The indications for intubation determined individually for each patient and clinical status.
• Death from any cause [ Time Frame: during hospitalization, up to 30 days ]
  Death from any cause during hospitalization.
• Change in serum interleukin-6 concentration from day 0 to day 3 [ Time Frame: 3 days from randomization ]
  Primary laboratory endpoint.
• Change in serum interleukin-6 concentration from day 0 to day 7 [ Time Frame: 7 days from randomization ]
  Primary laboratory endpoint.

Current Secondary Outcome Measures (submitted: June 27, 2022)

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

Original Secondary Outcome Measures (submitted: June 24, 2021)

• The time of invasive mechanical ventilation [ Time Frame: during hospitalization, up to 30 days ]
  Defined as the number of days between intubation and extubation.
• The time with Non-invasive mechanical ventilation (NIV) or High-flow nasal cannula (HFNC) [ Time Frame: 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).
• The time with oxygen therapy [ Time Frame: during hospitalization, up to 30 days ]
  Defined as the number of days of oxygen therapy (including all methods of oxygen therapy)
• The duration of hospitalization [ Time Frame: during hospitalization, up to 30 days ]
  Defined as the number of days that pass between the day of hospital admission and discharge or death.
• Discontinuation of oxygen therapy before discharge [ Time Frame: during hospitalization, up to 30 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19
• Official Title: 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.
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sars-CoV-2 Infection

Intervention

• Drug: Evolocumab
  A single subcutaneous administration of 140 mg evolocumab
• Drug: Saline solution
  A single subcutaneous injection of 1ml of 0,9% saline solution

Study Arms

• Experimental: PCSK9 inhibitor (evolocumab)
  140 mg of evolocumab as a single subcutaneous injection and standard of care accordance to the latest recommendations
  Intervention: Drug: 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.
  Intervention: Drug: Saline solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 24, 2021): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 17, 2022
• Actual Primary Completion Date: May 17, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT04941105
• Other Study ID Numbers: IMPACT-SIRIO 5
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jacek Kubica, Collegium Medicum w Bydgoszczy
• Original Responsible Party: Same as current
• Current Study Sponsor: Collegium Medicum w Bydgoszczy
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Collegium Medicum w Bydgoszczy
• Verification Date: April 2023