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

NCT04941105 | Completed Phase 3 DMC

• 1 other identifier: IMPACT-SIRIO 5
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Sars-CoV-2 Infection

Keywords

COVID-19; SARS-CoV-2 Pneumonia; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

  during hospitalization, up to 30 days

• Need for intubation

  during hospitalization, up to 30 days

• Duration of oxygen therapy

  during hospitalization, up to 30 days

• Duration of hospital stay

  during hospitalization, up to 30 days

Study Arms (2)

PCSK9 inhibitor (evolocumab)

EXPERIMENTAL

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

Drug: Evolocumab

Usual Care

PLACEBO COMPARATOR

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

Interventions

Evolocumab DRUG

A single subcutaneous administration of 140 mg evolocumab

PCSK9 inhibitor (evolocumab)

Saline solution DRUG

A single subcutaneous injection of 1ml of 0,9% saline solution

Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Use of fibrates other than fenofibrate or fenofibric acid
• Known active infections or other clinical condition that contraindicate PCSK9 inhibitors
• Known systemic hypersensitivity to PCSK9 inhibitors
• Estimated glomerular filtration rate \<30 ml/min/1.73 m2
• Absolute neutrophil count (ANC) less than 2000/mm3
• A platelet count less than 50000/mm3
• Creatine kinase (CK) greater than 3x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3x upper limit of normal (ULN)
• Not expected to survive for more than 48 hours from screening
• Unrelated co-morbidity with life expectancy \<3 months.
• Pregnancy
• 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
• Patient being treated with other immunomodulators (except for glucocorticoids).
• Patient included in any other interventional trial.

Sponsors & Collaborators

• Collegium Medicum w Bydgoszczy: lead

Study Sites (1)

Antoni Jurasz University Hospital No. 1

Bydgoszcz, Poland

Location

Related Publications (1)

• Navarese EP, Podhajski P, Gurbel PA, Grzelakowska K, Ruscio E, Tantry U, Magielski P, Kubica A, Niezgoda P, Adamski P, Junik R, Przybylski G, Pilaczynska-Cemel M, Rupji M, Specchia G, Pinkas J, Gajda R, Gorog DA, Andreotti F, Kubica J. PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection. J Am Coll Cardiol. 2023 Jan 24;81(3):224-234. doi: 10.1016/j.jacc.2022.10.030.

  PMID: 36653090 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

evolocumab; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jacek Kubica, MD, PhD

  Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

  PRINCIPAL INVESTIGATOR

• Eliano Navarese, Md, PhD

  Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Cardiology and Internal Medicine

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 28, 2021
• Study Start: June 1, 2021
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: April 21, 2023

Record last verified: 2023-04

Locations

PL (1)