Bivalirudin Versus Enoxaparin in Critically Ill COVID-19 Patients

Bivalirudin Versus Enoxaparin for Anticoagulation in Critically Ill COVID-19 Patients: a Pilot Randomized Controlled Trial

Coronavirus Disease (COVID-19) is characterized by a hypercoagulable state, sometimes difficult to be managed with heparin. Bivalirudin, a member of the direct thrombin inhibitor drug class, offers potential advantages compared to heparin, including to its ability to exert its effect by directly attaching to and inhibiting freely circulating and fibrin-bound thrombin.

Investigators have therefore designed this pilot open-label randomized controlled trial to assess if a off-label infusion of bivalirudin may reduce thrombosis, mortality, Intensive Care Unit (ICU) length of stay and increase ventilator free days of patients admitted in ICU for acute respiratory failure due to COVID-19, as compared to first-line treatment with heparin.

Study Overview

• Status: Completed
• Conditions: SARS CoV 2 Infection; Acute Respiratory Failure; Anticoagulants
• Intervention / Treatment: Drug: Enoxaparin Sodium; Drug: Bivalirudin

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy
    • AOU Mater Domini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ratio between arterial partial pressure to inspired fraction of oxygen (PaO2/FiO2) < 200 mmHg
• age equal or greater of 18 years/old
• detection of coronavirus 2019 at the nasal swab;
• need for endotracheal intubation and invasive mechanical ventilation

Exclusion Criteria:

• known allergies to one of the two investigated drugs
• presence of hematological diseases
• pregnancy
• recent (10 days) surgery
• presence of active bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin sodium; Enoxaparin sodium twice daily, according to the renal function and clinical indication	Drug: Enoxaparin Sodium; Enoxaparin will be subcutaneously administered at a dosage from 4000 to 8000 twice daily according
Experimental: Bivalirudin; Bivalirudin will be administered by continuous infusion, until day 7. Bivalirudin will be administered at dosage of 0,25 mg/kg in first 30 minutes, followed by continuous infusion of 0,2 mg/kg/h until 7 days. The infusion rate will be adjusted targeting a prothrombin time ratio of about 1.5.	Drug: Bivalirudin; Bivalirudin will be intravenously administered to obtain an activated prothrombin time (aPTT) of 1.5 fold of the normal values.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent under invasive mechanical ventilation	number of days that patient would require invasive mechanical ventilation	from randomization till 28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of vein thrombosis and embolism	Number of patients with diagnosis of deep vein thrombosis and/or pulmonary embolism	from randomization till 28 days after randomization or ICU discharge
Gas Exchange	Daily evaluation of oxygenation through arterial blood gases	Every day till 28 days after randomization or ICU discharge
Intensive Care Unit length of stay	Number of days spent in Intensive Care Unit	Up to 1 year
Intensive Care Unit mortality	Number of patients died during the Intensive Care Unit stay	Up to 1 year

Collaborators and Investigators

• Sponsor: University Magna Graecia

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2022
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): July 30, 2022

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 15, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Bivalirudin; Enoxaparin; Enoxaparin sodium
• Other Study ID Numbers: Bivalirudin COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual patients data will be shared only after the publication of the study on an international peer-reviewed journal and on scientific and intelligible proposal
• IPD Sharing Time Frame: Data will be available after publication on an indexed international and peer-reviewed journal
• IPD Sharing Access Criteria: Access will be allowed after contacting by email the principal investigator, by providing and intelligible and scientific proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No