Impact of an Intensified Thromboprofylaxis Protocol in COVID-19

Study Overview
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Brief Summary
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The aim of this study is to investigate and compare the mortality, the incidence of DVT and the incidence of kidney and liver failure in patients admitted to the ICU before and after the implementation of an intensified thromboprofylaxis protocol on 31st of March 2020. Patients in the before group are admitted at the ICU from 13/3/2020-30/3/2020 and patients in the after group are admitted to the ICU from 31/3 until 20/4/2020.

Detailed Description
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Background Patients admitted to the Intensive Care Unit (ICU) are known to be at risk for thrombo-embolic events. Virchow's triad describes the major risk factors in three categories: venous stasis, vessel injury and activation of blood coagulation. A prolonged mechanical ventilation together with the hemodynamic effects of this ventilation with a high positive and expiratory pressure (PEEP), the presence of central venous catheters, the immobilization of these patients and the presence of obesity or other comorbidities can attribute to the occurrence of a deep venous thrombosis (DVT) in patients admitted at ICU. The incidence of DVT during ICU stay has been reported between 5 and 15%. On the 13th of March, the first COVID-19 patient was admitted at the ICU at the Jessa Hospital. Within a few days, the admissions at our COVID-19 unit grew exponential. In these difficult time, research concerning COVID-19 has been performed indicating the COVID-19 virus induces a hyper-inflammatory state. It has been suggested that systemic inflammation induces endothelial injury. This will activate the coagulation cascade and impair fibrinolysis with disruption of endothelial barrier, and loss of physiologic antithrombotic factors which may elevated the risk for DVTs significantly. Up to now, there is still no causal treatment for COVID-19. The current management of COVID-19 is mainly supportive i.e. a prolonged inflammatory status and a prolonged risk for VTE. We have shown in a previous cross sectional study that the prevalence of deep venous thrombosis (DVT) in critically ill ICU patients with COVID-19 treated with a prophylactic dose of low molecular weight heparin (LMWH) is more than 60% (submitted manuscript). Consequently, the risk of VTE complications in this patient group is very high. In the light of these findings, an intensified thromboprofylaxis protocol was applied in critically ill ICU patients with COVID-19 at our ICU units since 31st of March 2020. Aim The aim of this study is to investigate and compare the mortality, the incidence of DVT and the incidence of kidney and liver failure in patients admitted to the ICU before and after the implementation of an intensified thromboprofylaxis protocol on 31st of March 2020. Patients in the before group are admitted at the ICU from 13/3/2020-30/3/2020 and patients in the after group are admitted to the ICU from 31/3 until 20/4/2020. Design This is a retrospective, longitudinal, before-after controlled study investigating the mortality, the incidence of DVT and the incidence of kidney and liver failure in COVID-19 patients admitted to the ICU before and after the implementation of an intensified thromboprofylaxis protocol. Outcome measures The primary endpoint of this retrospective study is to investigate the mortality in critically ill ICU patients before and after the implementation of the intensified thromboprofylaxis protocol in our hospital. Secondary endpoints are the incidence of DVTs with the number and locations of these thromboses, the incidence of kidney failure and the incidence of liver failure in COVID-19 patients admitted to the ICU before and after the implementation of the thromboprofylaxis protocol. Additional data collection Additional collected parameters are listed below and are collected as a standard-of-care in our hospital: Demographics: i.e age, gender, BMI, Apache II score (to predict mortality) Comorbidities: smoking, obesity, hypertension, diabetes, cardiovascular disease, respiratory disease, malignancies, renal failure (AKI), liver failure, gastrointestinal disease, neurological conditions, mental state, other Symptoms at the time of admission to ICU: i.e fever, body temperature, dyspnoea, headache, diarrhea etc… Laboratory results of all standard parameters measured Treatment: antiviral agents, antibiotics, etc… Complications: shock, heart failure, sepsis, stroke, etc… Ventilation: method, PEEP, FiO2, P/F ratio .. SOFA score (Sequential Organ Failure Assessment) Radiological findings: pneumonia, ground-glass opacity..

Official Title
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Impact of Implementation of an Intensified Thromboprofylaxis Protocol in in Critically Ill ICU Patients With COVID-19: a Longitudinal Controlled Before-after Study

Conditions
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COVID19, Thromboembolism

Intervention / Treatment
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* Other: thromboprofylaxis protocol
* Other: standard protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - All adult COVID19+ patients admitted to the ICU from 13th of March until 20th of April 2020. Exclusion Criteria: - Patients younger than 18 years old.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Before or control group<br>All patients admitted to ICU from March 13th 2020 until March 30th 2020 received routine low dose pharmacological VTE prophylaxis | Other: standard protocol<br>* This protocol contains a routine low dose pharmacological venous thromboembolism (VTE) prophylaxis with LMWH<br>|
| After or intervention group<br>On March 31th 2020 an individualised, more aggressive thromboprophylaxis protocol was implemented. This individualised protocol contains three cornerstones: an increase in dosage of prophylactic LMWH close to therapeutic doses, introduction of routine venous ultrasonography and daily measurements of plasma anti-factor Xa activity | Other: thromboprofylaxis protocol<br>* This individualised protocol contains three cornerstones: an increase in dosage of prophylactic LMWH close to therapeutic doses, introduction of routine venous ultrasonography and daily measurements of plasma anti-factor Xa activity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 week mortality | mortality was assessed in all COVID 19 patients admitted to the ICU | 2 weeks after admission at ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of venous thromboembolism | the incidence of venous thromboembolism was evaluated in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| 1 week mortality | mortality was assessed in all COVID 19 patients admitted to the ICU | 1 week after admission at ICU | 
| 3 week mortality | mortality was assessed in all COVID 19 patients admitted to the ICU | 3 weeks after admission at ICU | 
| 1 month mortality | mortality was assessed in all COVID 19 patients admitted to the ICU | 1 month after admission at ICU | 
| incidence of kidney failure | incidence of acute kidney failure in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| incidence of continuous renal replacement therapy (CRRT) | incidence of continuous renal replacement therapy (CRRT) in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| lowest PaO2/FiO2 (P/F) ratio | evaluation of the lowest P/F ratio in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| highest Sequential Organ Failure Assessment (SOFA) score | evaluation of the highest SOFA score in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| length of stay | evaluation of the length of stay in ICU and hospital of all COVID 19 patients admitted to the ICU | during ICU and hospital stay up till 3th of May 2020 | 
| highest bilirubin | evaluation of the highest bilirubine level in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| highest ( AST | evaluation of the highest AST level in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 | 
| highest Aspartaat-Amino-Transferase (ALT) | evaluation of the highest ALT level in all COVID 19 patients admitted to the ICU | during ICU stay up till 3th of May 2020 |