Clinical trial NCT04394000: Impact of an Intensified Thromboprofylaxis Protocol in COVID-19
Official title: Impact of Implementation of an Intensified Thromboprofylaxis Protocol in in Critically Ill ICU Patients With COVID-19: a Longitudinal Controlled Before-after Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID19
Thromboembolism
Lead sponsor: Jessa Hospital
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: All adult COVID19+ patients admitted to the ICU from 13th of March until 20th of April 2020.

Brief summary: 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: 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..

Eligibility criteria: 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.

Primary outcomes:
measure: 2 week mortality
timeFrame: 2 weeks after admission at ICU
Secondary outcomes:
measure: incidence of venous thromboembolism
timeFrame: during ICU stay up till 3th of May 2020
measure: 1 week mortality
timeFrame: 1 week after admission at ICU
measure: 3 week mortality
timeFrame: 3 weeks after admission at ICU
measure: 1 month mortality
timeFrame: 1 month after admission at ICU
measure: incidence of kidney failure
timeFrame: during ICU stay up till 3th of May 2020
measure: incidence of continuous renal replacement therapy (CRRT)
timeFrame: during ICU stay up till 3th of May 2020
measure: lowest PaO2/FiO2 (P/F) ratio
timeFrame: during ICU stay up till 3th of May 2020
measure: highest Sequential Organ Failure Assessment (SOFA) score
timeFrame: during ICU stay up till 3th of May 2020
measure: length of stay
timeFrame: during ICU and hospital stay up till 3th of May 2020
measure: highest bilirubin
timeFrame: during ICU stay up till 3th of May 2020
measure: highest ( AST
timeFrame: during ICU stay up till 3th of May 2020
measure: highest Aspartaat-Amino-Transferase (ALT)
timeFrame: during ICU stay up till 3th of May 2020
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa hospital
Study officials:
References:
citation: Stessel B, Vanvuchelen C, Bruckers L, Geebelen L, Callebaut I, Vandenbrande J, Pellens B, Van Tornout M, Ory JP, van Halem K, Messiaen P, Herbots L, Ramaekers D, Dubois J. Impact of implementation of an individualised thromboprophylaxis protocol in critically ill ICU patients with COVID-19: A longitudinal controlled before-after study. Thromb Res. 2020 Oct;194:209-215. doi: 10.1016/j.thromres.2020.07.038. Epub 2020 Jul 22.