Enhanced Platelet Inhibition in Critically Ill Patients With COVID-19

NCT04368377 | Completed Phase 2 DMC

• 1 other identifier: 18275/2020
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).

Conditions

Pneumonia, Viral; Corona Virus Infection; Respiratory Failure; Embolism and Thrombosis

Keywords

Covid-19; Pneumonia; Respiratory failure; Platelet inhibition; GP IIb/IIIa inhibitor; Thrombosis; Platelet disfunction

Outcome Measures

Primary Outcomes (3)

• P/F ratio

  Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment

  At baseline and 24, 48 and 168 hours after treatment initiation

• PaO2 difference

  Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

  At baseline and 24, 48 and 168 hours after treatment initiation

• A-a O2 difference

  Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.

  At baseline and 24, 48 and 168 hours after treatment initiation

Secondary Outcomes (8)

• CPAP duration

  From the first day of study drugs administration (T0) until day 7 post study drugs administration

• In-hospital change in intensity of the respiratory support

  At baseline and 72 and 168 hours after treatment initiation

• PaCO2 difference

  At baseline and 24, 48 and 168 hours after treatment initiation

• HCO3- difference

  At baseline and 24, 48 and 168 hours after treatment initiation

• Lactate difference

  At baseline and 24, 48 and 168 hours after treatment initiation

Study Arms (1)

Tirofiban

EXPERIMENTAL

1. Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0.15 microgram/kg/minute for 48 hours. 2. Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75 mg daily for 30 days. 3. Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75 mg daily for 30 days 4. Patents will receive concurrent fondaparinux 2.5 mg s/c per day for the duration of the hospital stay

Drug: Tirofiban Injection; Drug: Clopidogrel; Drug: Acetylsalicylic acid; Drug: Fondaparinux

Interventions

Tirofiban Injection DRUG

Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0,15 microgram/kg//minute for 48 hours.

Also known as: Ibisqus, Agrastat

Tirofiban

Clopidogrel DRUG

Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75mg daily for 30 days

Also known as: Plavix

Tirofiban

Acetylsalicylic acid DRUG

Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75mg daily for 30 days.

Also known as: Cardirene

Tirofiban

Fondaparinux DRUG

Patients will receive concurrent fondaparinux 2.5mg s/c per day for the duration of the in hospital stay

Also known as: Arixtra

Tirofiban

Eligibility Criteria

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

You may qualify if:

• Laboratory-confirmed SARS-CoV-2-related pneumonia, defined as positive nasal swab for SARS-CoV-2 infection or positive IgM serum title. A laboratory confirmed diagnosis must be associated with a clinically confirmed COVID-19 pneumonia, with a history of fever ≥ 3 days and multiple pulmonary infiltrates at the chest X-Ray
• Acute de novo severe hypoxic respiratory failure, defined by means of arterial blood gas analysis performed in room air showing severe hypoxemia with an arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio \< 250 (according to the Berlin 2012 acute respiratory distress syndrome - ARDS - definition), requiring CPAP respiratory support
• D-Dimer value ≥ 3 times the upper level of normal of the laboratory

You may not qualify if:

• Ongoing bleeding or bleeding diathesis, contraindications for anticoagulation or increased bleeding risk or history of bleeding in the last eight weeks
• Previous stroke or transient ischemic attack or any intracranial pathology in the last six months, major surgery or trauma within the previous six weeks
• Laboratory confirmed Laboratory confirmed Glucose 6-Phosphate Dehydrogenase (G6PDH) deficiency.
• Confirmed or suspected pregnancy or patients in childbearing age.
• Previous known adverse effects or intolerance to the study drugs
• Ongoing septic shock. Septic shock will be defined as the concomitant presence of sepsis (life-threatening organ dysfunction caused by a dysregulated host response to infection with a Sequential \[Sepsis-related\] Organ Failure Assessment (SOFA) score of 2 points or more) and need for vasopressors to maintain a mean arterial pressure of 65 mm Hg or greater and a serum lactate level greater than 2 mmol/L (\>18 mg/dL) in the absence of hypovolemia.
• Need for surgery during hospitalization
• Elevated risk of in hospital fall
• Glasgow Coma Scale \<15
• Confirmed diagnosis of dementia or mental disability that jeopardizes the comprehension of the study protocol
• Inability to sign the informed consent

Sponsors & Collaborators

• University of Milan: lead
• Fondazione "Un Cuore per Milano" - a no profit foundation: collaborator

Study Sites (1)

L. Sacco Hospital

Milan, Lombardy, 20157, Italy

Location

Related Publications (2)

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

  PMID: 33502773 DERIVED

MeSH Terms

Conditions

Pneumonia, Viral; Coronavirus Infections; Respiratory Insufficiency; Embolism and Thrombosis; COVID-19; Pneumonia; Thrombosis

Interventions

Tirofiban; Clopidogrel; Aspirin; Fondaparinux

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiration Disorders; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Oligosaccharides; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Respiratory Medicine

Model Details: Compassionate-use, proof of concept, interventional, prospective,

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 29, 2020
• Study Start: April 6, 2020
• Primary Completion: April 23, 2020
• Study Completion: April 23, 2020
• Last Updated: April 29, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)