Bivalirudin Versus Enoxaparin in Critically Ill COVID-19 Patients

Sponsor

University Magna Graecia (Other)

Overall Status

Completed

CT.gov ID

NCT05334654

Collaborator

(none)

Enrollment

Location

Arms

3.3

Actual Duration (Months)

17.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Failure SARS CoV 2 Infection Anticoagulants	Drug: Enoxaparin Sodium Drug: Bivalirudin	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Investigators and Outcome assessors will not take part in the care of patients. Data will be provide in anonymous form without any indication to the assigned treatment.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 20, 2022

Actual Primary Completion Date :

Jun 30, 2022

Actual Study Completion Date :

Jul 30, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Time spent under invasive mechanical ventilation [from randomization till 28 days after randomization]
number of days that patient would require invasive mechanical ventilation

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AOU Mater Domini	Catanzaro		Italy

Sponsors and Collaborators

University Magna Graecia

Investigators

Principal Investigator: Federico Longhini, MD, Magna Graecia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Federico Longhini, Director of the Intensive Care and Anesthesia Department, University Magna Graecia

ClinicalTrials.gov Identifier:

NCT05334654

Other Study ID Numbers:

Bivalirudin COVID-19

First Posted:

Apr 19, 2022

Last Update Posted:

Aug 19, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

COVID-19

Respiratory Insufficiency

Enoxaparin

Enoxaparin sodium

Bivalirudin

Study Results

No Results Posted as of Aug 19, 2022