Acetylsalicylic Acid in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients With COVID-19

NCT04808895 | Unknown Phase 3

• 1 other identifier: EudraCT 2020-006130-12
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence, and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of acetylsalicylic acid may improve inflammation and respiratory function in humans as indicated by the results of observational studies. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider acetylsalicylic acid for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of antiplatelet agents and the evidence of improvement in respiratory function both in human and experimental pathology. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with acetylsalicylic acid could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs), except for specific contraindications. To this aim, the investigators a randomised, placebo-controlled, double blind, parallel arms study to investigate the potential protection of acetylsalicylic acid towards the progression of lung failure in patients admitted to a medical ward for SARS-CoV-2 pneumonia. A 15-day treatment period is considered. Primary endpoint is the occurrence of one of the following events: admission to an intensive care unit, requirement of mechanical ventilation, PaO2/FiO2 less than 150 mm Hg.

Conditions

COVID-19; Thrombosis Pulmonary

Keywords

Acetylsalicylic acid; Heparin; Pulmonary thrombosis; COVID-19; Platelets; Inflammation; Respiratoty failure

Outcome Measures

Primary Outcomes (3)

• Prevention of clinical worsening

  Transfer to ICU

  day 15

• Prevention of lung function worsening

  PaO2/FiO2 lower than 150 mm Hg

  day 15

• Prevention of death

  Death for any cause

  day 15

Secondary Outcomes (45)

• Change in body temperature

  Daily for 15 days

• Change in oxygen saturation

  Daily for 15 days

• Change in blood gases

  Daily for 15 days

• Change in blood cell count

  Daily for 15 days

• Change in blood oxygen

  Daily for 15 days

Study Arms (2)

Acetylsalicylic acid

ACTIVE COMPARATOR

Tablets of 100 mg acetylsalicylic acid (one 100 mg daily dose. On the first day a loading dose of 300 mg will be administered)

Drug: Acetylsalicylic acid

Placebo

PLACEBO COMPARATOR

Tablets of placebo, identical to active comparator (one tablet daily dose. On the first day 3 tablets will be administered)

Drug: Placebo

Interventions

Acetylsalicylic acid DRUG

administration of one tablet daily for 15 days. On the first day a loading dose of 300 mg will be administered

Acetylsalicylic acid

Placebo DRUG

administration of one tablet daily for 15 days. On the first day 3 tablets will be administered

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• in a medical area ward dedicated to Covid-19 patients
• Positivity by RT\_PCR of the search for genetic material of SARS-CoV2
• Covid-19 pneumonia with moderate clinical picture based on clinical parameters
• O2 saturation\> 94% with maximum FiO2 32%
• Respiratory acts \<30 / minute
• age \>18 years
• Consent to participate in the study

You may not qualify if:

• Any Antithrombotic treatment including acetylsalicylic acid
• Active Bacterial infection
• Active or in maintenance therapy neoplasm
• Inability to provide consent
• Any contraindication to the acetylsalicylic acid use
• Active peptic disease
• Active Major pathological bleeding
• Recent (\<30 days) major bleeding
• Recent intracranial bleeding
• Need to use therapeutic doses of oral anticoagulants or heparins
• Need to use combination antiplatelet drugs for clinical indication
• Hypersensitivity to acetylsalicylic acid or to any of the excipients
• Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)
• Severe hepatic insufficiency (Child-Pugh class C).
• Severe heart failure (NYHA class 3-4)

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead

Study Sites (1)

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

Related Publications (27)

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MeSH Terms

Conditions

COVID-19; Inflammation

Interventions

Aspirin

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Pietro Minuz, Professor

  University of Verona, AOUI Verona

  STUDY DIRECTOR

• Marco Cattaneo, Professor

  University of Milan

  STUDY DIRECTOR

• Roberto Leone, Professor

  Universita di Verona

  STUDY DIRECTOR

Central Study Contacts

Pietro Minuz, Professor

CONTACT

+39 045-8124414; pietro.minuz@univr.it

Marco Cattaneo, Professor

CONTACT

+390250323095; marco.cattaneo@unimi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Use of placebo tablets of the same shape, colour of the investigational drug. Identical time and route of administration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental phase 3 drug trial, randomized 1:1, double-blind, multicentre in patients treated with acetylsalicylic acid vs placebo.

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 22, 2021
• Study Start: April 1, 2021
• Primary Completion: July 1, 2021
• Study Completion: August 31, 2021
• Last Updated: March 22, 2021

Record last verified: 2021-03

Locations

IT (1)