AnaConDa-therapy in COVID-19 Patients

COVID-19 Clinical Trial

Official title:

AnaConDa-therapy in COVID-19 Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05586126
• Other study ID #: 2020.10.15.03
• Status: Terminated
• Start date: October 1, 2020
• Est. completion date: July 1, 2022

Study information

• Verified date: October 2022
• Source: Jeroen Bosch Ziekenhuis
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: July 1, 2022
• Est. primary completion date: January 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS CoV-2

Intervention

Drug:
• Sevoflurane
sevoflurane inhalation

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch	Noord Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Jeroen Bosch Ziekenhuis

Country where clinical trial is conducted

Netherlands, 

References & Publications (17)

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Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall JR, Morris A, Spragg R. Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med. 1994;20(3):225-32. Review. — View Citation

Bisbal M, Arnal JM, Passelac A, Sallée M, Demory D, Donati SY, Granier I, Corno G, Durand-Gasselin J. [Efficacy, safety and cost of sedation with sevoflurane in intensive care unit]. Ann Fr Anesth Reanim. 2011 Apr;30(4):335-41. doi: 10.1016/j.annfar.2011.01.019. Epub 2011 Mar 15. French. — View Citation

Burki T. The origin of SARS-CoV-2. Lancet Infect Dis. 2020 Sep;20(9):1018-1019. doi: 10.1016/S1473-3099(20)30641-1. — View Citation

Ferrando C, Aguilar G, Piqueras L, Soro M, Moreno J, Belda FJ. Sevoflurane, but not propofol, reduces the lung inflammatory response and improves oxygenation in an acute respiratory distress syndrome model: a randomised laboratory study. Eur J Anaesthesiol. 2013 Aug;30(8):455-63. doi: 10.1097/EJA.0b013e32835f0aa5. — View Citation

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. — View Citation

Grifoni E, Valoriani A, Cei F, Lamanna R, Gelli AMG, Ciambotti B, Vannucchi V, Moroni F, Pelagatti L, Tarquini R, Landini G, Vanni S, Masotti L. Interleukin-6 as prognosticator in patients with COVID-19. J Infect. 2020 Sep;81(3):452-482. doi: 10.1016/j.jinf.2020.06.008. Epub 2020 Jun 8. — View Citation

Jabaudon M, Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L, Thibault S, Blondonnet R, Clairefond G, Guérin R, Perbet S, Cayot S, Godet T, Pereira B, Sapin V, Bazin JE, Futier E, Constantin JM. Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):792-800. doi: 10.1164/rccm.201604-0686OC. — View Citation

Jerath A, Ferguson ND, Cuthbertson B. Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med. 2020 Aug;46(8):1563-1566. doi: 10.1007/s00134-020-06154-8. Epub 2020 Jun 25. Review. — View Citation

Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile Anesthetics. Is a New Player Emerging in Critical Care Sedation? Am J Respir Crit Care Med. 2016 Jun 1;193(11):1202-12. doi: 10.1164/rccm.201512-2435CP. Review. — View Citation

Kellner P, Müller M, Piegeler T, Eugster P, Booy C, Schläpfer M, Beck-Schimmer B. Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury. Anesth Analg. 2017 Jan;124(1):194-203. — View Citation

Mesnil M, Capdevila X, Bringuier S, Trine PO, Falquet Y, Charbit J, Roustan JP, Chanques G, Jaber S. Long-term sedation in intensive care unit: a randomized comparison between inhaled sevoflurane and intravenous propofol or midazolam. Intensive Care Med. 2011 Jun;37(6):933-41. doi: 10.1007/s00134-011-2187-3. Epub 2011 Mar 29. — View Citation

O'Gara B, Talmor D. Lung protective properties of the volatile anesthetics. Intensive Care Med. 2016 Sep;42(9):1487-9. doi: 10.1007/s00134-016-4429-x. Epub 2016 Jul 4. Review. — View Citation

Perbet S, Bourdeaux D, Sautou V, Pereira B, Chabanne R, Constantin JM, Chopineau J, Bazin JE. A pharmacokinetic study of 48-hour sevoflurane inhalation using a disposable delivery system (AnaConDa®) in ICU patients. Minerva Anestesiol. 2014 Jun;80(6):655-65. Epub 2013 Nov 13. — View Citation

Soukup J, Selle A, Wienke A, Steighardt J, Wagner NM, Kellner P. Efficiency and safety of inhalative sedation with sevoflurane in comparison to an intravenous sedation concept with propofol in intensive care patients: study protocol for a randomized controlled trial. Trials. 2012 Aug 10;13:135. doi: 10.1186/1745-6215-13-135. — View Citation

Strosing KM, Faller S, Gyllenram V, Engelstaedter H, Buerkle H, Spassov S, Hoetzel A. Inhaled Anesthetics Exert Different Protective Properties in a Mouse Model of Ventilator-Induced Lung Injury. Anesth Analg. 2016 Jul;123(1):143-51. doi: 10.1213/ANE.0000000000001296. — View Citation

Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 May;163(6):1376-83. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P/F ratio	arterial oxygen tension divided by fraction of inspired oxygen	day 2 after intubation
Secondary	duration of ICU admission	number of days of admission	through ICU admission
Secondary	28VFD	number of ventilator-free days after 28 days	28 days after intubation
Secondary	28DFD	number of delirium-free days after 28 days	28 days after intubation
Secondary	need for vasopressors	cumulative dosage per day	duration of ICU stay
Secondary	28DM	mortality after 28 days	28 days after intubation
Secondary	P/F ratio day 5	P/F ratio on day 5 after intubation	day 5 after intubation