Clinical trial NCT05586126: AnaConDa-therapy in COVID-19 Patients
Official title: AnaConDa-therapy in COVID-19 Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: COVID-19
SARS CoV-2
Keywords: sevoflurane
propofol
midazolam
COVID-19
Lead sponsor: Jeroen Bosch Ziekenhuis
Sponsor class: OTHER
First posted: 2022-10-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients with proven COVID-19 and need for invasive mechanical ventilation in the ICU of the Jeroen Bosch Hospital

Brief summary: COVID 19-pneumonia may evolve into respiratory insufficiency for which invasive mechanical ventilation is required. Recently, inhaled anesthetics have become available for sedation of critically ill patients. Based upon recent research, these anesthetics may provide advantages in improvement of P/F ratio in ARDS patients. However, up to now, its effects on COVID-19 pneumonia patients is unknown; therefore, this study was designed as a plan to investigate whether the use of inhaled sevoflurane leads to improvement of oxygenation compared to intravenous sedatives in mechanically ventilated COVID-19 patients

Detailed description: COVID-19 is an infectious disease caused by the virus SARS-CoV-2, which can lead to severe pneumonia with acute respiratory distress syndrome (ARDS)-like presentation. In this condition, the exchange of oxygen and carbon dioxide in the lungs is compromised because of an inflammatory response with capillary leak. This leads to deterioration of oxygenation with hypoxemia and a decrease in P/F (arterial oxygen tension/fraction of inspired oxygen) ratio, resulting in need for invasive mechanical ventilation. To accomplish this, the patient needs to be sedated. Classic, intravenous sedatives usually come with long half-lifes, which lead to prolonged need for mechanical ventilation, because of residual sedation. Next to short half-life, the inhalation anesthetic sevoflurane is supposed to have anti-inflammatory effects, which could improve oxygenation.

This study is designed to investigate the hypothesis that sedation by use of sevoflurane leads to better oxygenation in COVID-19 patients, compared to intravenous sedatives.

Secondarily, the effects of sevoflurane compared to intravenous sedatives on duration of admission and mechanical ventilation, on respiratory parameters and hemodynamics, inflammatory parameters, use of opioids, manner of waking up and prevalence of delirium, will be investigated.

Study design: The study concerns a single center cohort study in the ICU of the Jeroen Bosch Hospital in The Netherlands. Inhaled anesthesia by sevoflurane is compared to intravenous sedation. Both are considered to be standard of care.

Study population: Patients with respiratory insufficiency due to COVID-19 pneumonia, with need for invasive mechanical ventilation on the ICU in the Jeroen Bosch Hospital.

Study parameters: Primary outcome is P/F ratio (arterial oxygen tension/fraction of inspired oxygen; PaO2/FiO2 ratio) on day 2 and day 5. Secondary outcomes are duration of ICU admission, number of ventilator-free days after 28 days (28VFD), inflammation parameters (CRP/PCT), quality of waking up, number of delirium free days after 28 days (28DFD) and need for vasopressors. Also patient characteristics like demographic information (age, sex, BMI, comorbidity), respiratory and hemodynamic values and use of other sedatives will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* More than 24 hours of invasive mechanical ventilation needed
* Positive test (e.g. Polymerase Chain Reaction (PCR)) for SARS-CoV-2

Exclusion Criteria:

* pulmonary history
* known allergy or hypersensitivity for halogenated anesthetics
* known or suspected predisposition for malignant hyperthermia
* suspected or proven intracranial hypertension
* severe liver dysfunction and/or icterus (serum bilirubin \>42,8-51,3 μg per liter)
* neutropenia (\<0.5X10\^9 neutrophils per liter)
* chemotherapy in the month prior to ICU admission
* patients that are transported to other hospitals during admission

Primary outcomes:
measure: P/F ratio
timeFrame: day 2 after intubation
Secondary outcomes:
measure: duration of ICU admission
timeFrame: through ICU admission
measure: 28VFD
timeFrame: 28 days after intubation
measure: 28DFD
timeFrame: 28 days after intubation
measure: need for vasopressors
timeFrame: duration of ICU stay
measure: 28DM
timeFrame: 28 days after intubation
measure: P/F ratio day 5
timeFrame: day 5 after intubation
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
state: Noord Brabant
Study officials:
affiliation: Jeroen Bosch Hospital
name: D. van Nieuwenhuizen, RN
role: PRINCIPAL_INVESTIGATOR
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