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

• Sponsor: Collegium Medicum w Bydgoszczy (Other)
• Overall Status: Completed
• CT.gov ID: NCT04941105
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 2
• Actual Duration (Months): 11.5
• Patients Per Site Per Month: 5.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sars-CoV-2 Infection	Drug: Evolocumab; Drug: Saline solution	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Jun 1, 2021
• Actual Primary Completion Date: May 17, 2022
• Actual Study Completion Date: May 17, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Change in serum interleukin-6 concentration from day 0 to day 7 and day 30 [7 and 30 days from randomization]

2. Death from any cause [during hospitalization, up to 30 days]

   Death from any cause during hospitalization.

3. Need for intubation [during hospitalization, up to 30 days]

   Indication for intubation determined individually for each patient and clinical status

4. 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)

5. 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.

6. Days of intubation [during hospitalization, up to 30 days]

   Defined as the number of days between intubation and extubation

7. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Antoni Jurasz University Hospital No. 1	Bydgoszcz		Poland

Sponsors and Collaborators

• Collegium Medicum w Bydgoszczy

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jacek Kubica, Head of Department of Cardiology and Internal Medicine, Collegium Medicum w Bydgoszczy
• ClinicalTrials.gov Identifier: NCT04941105
• Other Study ID Numbers: IMPACT-SIRIO 5
• First Posted: Jun 28, 2021
• Last Update Posted: Jul 1, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jacek Kubica, Head of Department of Cardiology and Internal Medicine, Collegium Medicum w Bydgoszczy: COVID-19; SARS-CoV-2 Pneumonia; PCSK9 inhibitor
• Additional relevant MeSH terms: COVID-19; Evolocumab

Study Results

No Results Posted as of Jul 1, 2022