Tolerance and Efficacy of Amiklin Administration During Nosocomial Infections Complicating COVID-19 in the ICU

COVID-19 Clinical Trial

— ReaMax2  

Official title:

Tolerance and Efficacy of Amiklin Administration During Nosocomial Infections Complicating COVID-19 in the ICU

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05511129
• Other study ID #: ReaMax2
• Status: Active, not recruiting
• Start date: May 12, 2022
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2022
• Source: Groupe Hospitalier Paris Saint Joseph
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1053
• Est. completion date: June 30, 2023
• Est. primary completion date: June 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Cross Infection
• Infections
• Nosocomial Infection

Locations

Country	Name	City	State
France	Centre Hospitalier Bicetre	Paris
France	Groupe Hospitalier Paris Saint-Joseph	Paris
France	Hôpital Cochin	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Hospitalier Paris Saint Joseph

Country where clinical trial is conducted

France, 

References & Publications (9)

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. Epub 2004 Mar 2. — View 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. — View 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. — View 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. Review. — View 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. Review. — View 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. — View 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. — View Citation

Skorup P, Maudsdotter L, Lipcsey M, Larsson A, Sjölin 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changed risk of renal failure	This outcome corresponds to the evolution of renal function, calculated as the difference 1/ between the creatinine and urea values at entry and the maximum value and 2/ between the creatinine and urea values at entry and the value at discharge.	Month 3
Secondary	Effect of maximum serum concentration of Amikacin on renal function	This outcome corresponds to the percentage of patients with return to normal creatinine and urea values.	Month 3
Secondary	Effect of Amikacin administration on the probability of recovery of renal function	This outcome corresponds to the number of days between the maximum creatinine and urea value and normalization of the values. A "normal" value at discharge is defined as a value less than 1.25 times the entry value.	Month 3
Secondary	Effect of Amikacin administration on the rate of recovery of renal function	This outcome corresponds to the percentage of deaths during the resuscitation stay.	Month 3