Dosing of Thromboprophylaxis and Mortality in Critically Ill COVID-19 Patients

Dosing of Thromboprophylaxis and Mortality in Critically Ill COVID-19 Patients - More Patients Included and 90-day Follow up

The aim of the study is to associate dose of thromboprophylaxis with outcome in critically ill COVID-19 patients. This will be done by associating dose of thromboprophylaxis with 28-day mortality, survival outside ICU, thromboembolic event and bleeding complications.This was done in our earlier study for patients admitted in March and April (Clinicaltrials.gov NCT04412304 June 2 2020) but now we will include the patients admitted in May, June and half of July and we will ad the outcome of 90-day mortality.

Study Overview

• Status: Completed
• Conditions: Covid19; Thromboembolism
• Intervention / Treatment: Drug: Dose of tinzaparin or dalteparin

• Study Type: Observational
• Enrollment (Actual): 257

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 11883
    • Södersjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A cohort study of the critically ill Covid-19 patients admitted to ICU at Södersjukhuset, Stockholm from1st of March to 15 of July

Description

Inclusion Criteria:

• laboratory confirmed positive test for SARS-CoV-2
• admitted to ICU because of respiratory failure caused by Covid-19

Exclusion Criteria:

• patients with treatment for thromboembolic complications at arrival to the ICU
• short ICU length of stay defined as discharged the same date as ICU admission
• patients without initial thromboprophylaxis

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
low dose thromboprophylaxis; Daily dose of 2500-4500 IU tinzaparin or 2500-5000 IU dalteparin	Drug: Dose of tinzaparin or dalteparin; The patients will be categorised into three groups depending on initial dose of thromboprophylaxis in the ICU; Other Names: Innohep/Fragmin
medium dose thromboprophylaxis; Daily dose of >4500 IU but <175 IU/kg of body weight tinzaparin or >5000 IU but <200 IU/kg of body weight dalteparin	Drug: Dose of tinzaparin or dalteparin; The patients will be categorised into three groups depending on initial dose of thromboprophylaxis in the ICU; Other Names: Innohep/Fragmin
high dose thromboprophylaxis; Daily dose of ≥ 175 IU/kg of body weight tinzaparin or ≥200 IU/kg of body weight dalteparin	Drug: Dose of tinzaparin or dalteparin; The patients will be categorised into three groups depending on initial dose of thromboprophylaxis in the ICU; Other Names: Innohep/Fragmin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	28-day mortality from admission to ICU. Discontinue of ICU-care to palliative care counts as death.	28 days from ICU-admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of thromboembolic events	Thromboembolic events are defined as pulmonary emboli (PE), deep venous thrombus (DVT) and ischemic stroke. PE is defined as PE verified by computer tomography or by findings of acute strain of the right heart on echocardiography combined with a clinical interpretation of the patients deteriorating as a probable PE stated in the medical records. DVT is defined as DVT verified with ultrasound. Ischemic stroke is defined as ischemic stroke verified by computer tomography.	28 days from ICU-admission
Incidence of bleeding events	The event of bleeding will be defined by WHO modified bleeding scale as 1-4	28 days from ICU-admission
ICU-free days alive from ICU-admission	ICU-free days alive during 28 days from ICU-admission. Counts as 0 days if discharged to ward for palliative treatment.	28 days from ICU-admission
90-day mortality	90-day mortality from admission to ICU.	90 days from ICU-admission

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrin-D-dimer levels	Median value of Fibrin-D-dimer	28 days from ICU-admission

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Sandra Jonmarker, MD, Karolinska Institutet

Publications and helpful links

General Publications

• Jonmarker S, Litorell J, Dahlberg M, Stackelberg O, Everhov AH, Soderberg M, Rubenson-Wahlin R, Gunther M, Martensson J, Hollenberg J, Joelsson-Alm E, Cronhjort M. An observational study of intermediate- or high-dose thromboprophylaxis for critically ill COVID-19 patients. Acta Anaesthesiol Scand. 2022 Mar;66(3):365-374. doi: 10.1111/aas.14013. Epub 2021 Dec 16.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): August 15, 2020
• Study Completion (Actual): October 15, 2020

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 18, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Anticoagulation; Bleeding; Pulmonary embolism; Critical Care; Ischemic stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Embolism and Thrombosis; COVID-19; Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: Thromboprophylaxis COVID-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No