Clinical trial NCT05511129: Tolerance and Efficacy of Amiklin Administration During Nosocomial Infections Complicating COVID-19 in the ICU
Official title: Tolerance and Efficacy of Amiklin Administration During Nosocomial Infections Complicating COVID-19 in the ICU
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Nosocomial Infection
Lead sponsor: Fondation Hôpital Saint-Joseph
Sponsor class: OTHER
First posted: 2022-08-22
Enrollment: 1053
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with age ≥ 18 years, hospitalized for respiratory Covid-19 in the ICU or Respiratory Department for a PCR-confirmed respiratory infection with COVID-19

Brief summary: The most severe infectious episodes are managed in intensive care. Classically, a distinction is made between sepsis, an infection associated with an inappropriate, excessive response of the immune system, responsible for organ dysfunction, and septic shock, during which, within the potential dysfunctions, hemodynamic alteration is central, requiring the introduction of catecholamines. The seriousness of these disorders, particularly because of their potential short-term severity, requires immediate treatment. The treatment of severe infections is based on the control of microbial proliferation, particularly bacterial. In this context, the speed of antibiotic therapy is associated with patient prognosis. If the administration of antibiotic therapy is an emergency during severe infections, particularly in situations of septic shock, its choice is decisive in the effectiveness of management and in the prognosis of the patient. Prior to microbiological results, antibacterial treatment is probabilistic. In spite of these numerous parameters, failure of probabilistic antibiotic therapy, due to a spectrum unsuited to the pathogens, is described in 15 to 30% of cases. In order to limit the risk of inappropriate treatment, it is recommended that broad-spectrum antibiotic therapy be used in states of shock of infectious origin. Because of their bactericidal properties, their kinetics of effectiveness, their marked post-antibiotic effect, their bioavailability in the plasma sector, and their synergy with beta-lactams, aminoglycosides are often recommended in combination in the initial probabilistic treatment. Despite numerous studies and extensive international experience with aminoglycosides, their real value in the management of severe infections remains uncertain, leading to contradictory information depending on whether one is interested in their benefit in the treatment of identified infections or in the probabilistic treatment of severe conditions.

During the management of severe intensive care patients, the pharmacokinetics of drugs, especially antibiotics, are considerably modified. As a result, monitoring of plasma, or better, tissue concentrations of antibiotics is suggested by learned societies, although their practical realization is still very limited by numerous obstacles.

Misuse of aminoglycosides is associated with a risk of acute renal failure, centered on the tubular toxicity of the antibiotic. While the risks associated with inappropriate frequency of administration are currently modest, those associated with high peak concentration, responsible for an increase in the duration of renal exposure, are not well known.

COVID-19 is also associated with a high risk of impaired renal function. The effect of aminoglycoside administration in the context of COVID-19 remains unknown. Our goal is to determine whether the presence of COVID-19 associates with an elevated risk of renal failure when prescribing aminoglycoside.


Eligibility criteria: Inclusion Criteria:

* Patient with age ≥ 18 years
* Hospitalization for respiratory Covid-19
* Patient hospitalized in the ICU or Respiratory Department for a PCR-confirmed respiratory infection with COVID-19
* French-speaking patient

Exclusion Criteria:

* Patient with a severe psychiatric disorder
* A dying patient
* Patient under guardianship or curatorship
* Patient deprived of liberty
* Patient under court protection
* Patient objecting to the use of his or her data for this research

Primary outcomes:
measure: Changed risk of renal failure
timeFrame: Month 3
Secondary outcomes:
measure: Effect of maximum serum concentration of Amikacin on renal function
timeFrame: Month 3
measure: Effect of Amikacin administration on the probability of recovery of renal function
timeFrame: Month 3
measure: Effect of Amikacin administration on the rate of recovery of renal function
timeFrame: Month 3
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint-Joseph
city: Paris
country: France
facility: Centre Hospitalier Bicetre
city: Paris
country: France
facility: Hôpital Cochin
Study officials:
affiliation: Fondation Hôpital Saint-Joseph
name: François PHILIPPART, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
citation: Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA. 2018 Jan 2;319(1):62-75. doi: 10.1001/jama.2017.17687.
citation: Brun-Buisson C, Meshaka P, Pinton P, Vallet B; EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004 Apr;30(4):580-8. doi: 10.1007/s00134-003-2121-4. Epub 2004 Mar 2.
citation: Pletz MW, Blasi F, Chalmers JD, Dela Cruz CS, Feldman C, Luna CM, Ramirez JA, Shindo Y, Stolz D, Torres A, Webb B, Welte T, Wunderink R, Aliberti S. International Perspective on the New 2019 American Thoracic Society/Infectious Diseases Society of America Community-Acquired Pneumonia Guideline: A Critical Appraisal by a Global Expert Panel. Chest. 2020 Nov;158(5):1912-1918. doi: 10.1016/j.chest.2020.07.089. Epub 2020 Aug 25.
citation: Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
citation: Kumar A. Early antimicrobial therapy in severe sepsis and septic shock. Curr Infect Dis Rep. 2010 Sep;12(5):336-44. doi: 10.1007/s11908-010-0128-x.
citation: Seymour CW, Kahn JM, Martin-Gill C, Callaway CW, Yealy DM, Scales D, Angus DC. Delays From First Medical Contact to Antibiotic Administration for Sepsis. Crit Care Med. 2017 May;45(5):759-765. doi: 10.1097/CCM.0000000000002264.
citation: Whiles BB, Deis AS, Simpson SQ. Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients. Crit Care Med. 2017 Apr;45(4):623-629. doi: 10.1097/CCM.0000000000002262.
citation: Skorup P, Maudsdotter L, Lipcsey M, Larsson A, Sjolin J. Mode of bacterial killing affects the inflammatory response and associated organ dysfunctions in a porcine E. coli intensive care sepsis model. Crit Care. 2020 Nov 14;24(1):646. doi: 10.1186/s13054-020-03303-9.