Specific miRNAs in Sepsis and Nephrotoxic Antibiotic Treatment

Sepsis Clinical Trial

Official title:

Differentiation of Acute Kidney Injury in Sepsis and Due to Nephrotoxic Antibiotic Treatment With Vancomycin and Gentamicin Based on Measurements of Specific miRNAs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04991376
• Other study ID #: IK-01-miRNA
• Secondary ID: 01 - RVO - FNOs/
• Status: Completed
• Start date: May 2, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: December 2022
• Source: University Hospital Ostrava
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Critically ill patients are prone to develop acute kidney injury due to sepsis itself and by administration of potentially nephrotoxic antibiotic treatment (vancomycin or gentamicin). Blood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials.

Description:

Sepsis is generally defined as a life-threatening and dysregulated reaction to infection (bacterial, fungal, or viral) leading to systemic inflammation and organ dysfunction including acute kidney injury [1]. Acute kidney injury in critically ill patients is a common and usually serious condition associated with increased patient morbidity and mortality. Critically ill patients are prone to develop acute kidney injury due to sepsis itself and by administration of potentially nephrotoxic antibiotic treatment (vancomycin or aminoglycoside-gentamicin). To prevent nephrotoxicity and avoid subtherapeutic dosing, drug serum concentrations are usually monitored, with adjustment of dose or dosing interval according to the pharmacokinetic model. However, renal tubular injury can occur even if the treatment is optimally set. In the quest for new preventive or therapeutic targets (biomarkers) in septic/nephrotoxic acute renal damage, a current research focus in microRNAs. Based on data from previously published experimental and human studies we identified specific miRNAs associated with biochemical pathways involved in inflammation, organ ischemia, and nephrotoxicity with their exact determination and time-changing detection during the seven days in studied patients. Blood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials. Sampling method: Whole blood samples were taken on the first, fourth, and seventh days of antibiotic treatment. The first 24 samples (8 patients) were extracted in duplicate for screening of the selected miRNAs. Blood samples were collected into 2.5 mL tubes (Vacutainer® PAXgene, PreAnalytiX® GmbH, A Qiagen/BD Company, Switzerland). Concomitant-ly, the blood samples for NGAL determination were collected into 2.6 or 2 mL neutral tubes (S-Monovette® K3 EDTA, 2.6 mL, red, Sartstedt AG & Co. KG, Germany; or Vacuette® K3 EDTA 2 mL, violet, Greiner Bio-One GmbH, Germany). The blood samples for biochemical (renal and inflammatory) parameters (serum creatinine, interleukin-6, procalcitonin, C-reactive protein) were collected concomitantly with other dai-ly routine biochemical parameters (S-Monovette® serum-gel, 4.9 mL, brown, Sartstedt AG & Co. KG, Germany in University Hospital Ostrava; or Vacuette® serum-gel, 5.0 mL, red, Greiner Bio-One GmbH, Germany in University Hospital Olomouc). The serum antibiotic concentrations (vancomycin and gentamicin) were monitored according to standard care in both cooperating hospitals without needing more blood samples for study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 1, 2022
• Est. primary completion date: June 30, 2021
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• Critically ill adult septic patients with or without acute kidney injury treated by antimicrobial therapy

Exclusion Criteria:

• Patients in the chronic dialysis program, with stage 4 and 5 chronic kidney disease, or concomitantly treated with another potentially severe nephrotoxic medication (cisplatin, colistin) or combination vancomycin/gentamicin.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Sepsis
• Septic Shock
• Shock, Septic
• Toxemia

Intervention

Diagnostic Test:
• Blood-specific miRNA levels
Blood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials.

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital Ostrava	Palacky University, Technical University of Ostrava, University Hospital Olomouc, University of Ostrava

Country where clinical trial is conducted

Czechia, 

References & Publications (3)

Eckardt KU, Kasiske BL. Kidney disease: improving global outcomes. Nat Rev Nephrol. 2009 Nov;5(11):650-7. doi: 10.1038/nrneph.2009.153. Epub 2009 Sep 29. — View Citation

Petejova N, Martinek A, Zadrazil J, Kanova M, Klementa V, Sigutova R, Kacirova I, Hrabovsky V, Svagera Z, Stejskal D. Acute Kidney Injury in Septic Patients Treated by Selected Nephrotoxic Antibiotic Agents-Pathophysiology and Biomarkers-A Review. Int J Mol Sci. 2020 Sep 26;21(19):7115. doi: 10.3390/ijms21197115. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	miRNAs expression over 7 days of treatment	Determine and investigate specific circulating miRNAs linked to sepsis itself, septic, ischemic, or nephrotoxic acute kidney injury in patients suffered from sepsis. Tracking changes in miRNAs expression over 7 days of treatment with nephrotoxic (vancomycin or gentamicin) as compared with other, non-nephrotoxic antibiotic treatment.	7 days
Secondary	Association between circulating miRNA expression and serum neutrophil gelatinase-associated lipocalin (NGAL) and other renal or inflammatory markers	Association between circulating miRNA expression and serum neutrophil gelatinase-associated lipocalin (NGAL) and other renal or inflammatory markers to assess the potential of these small RNAs as pathophysiological biomarkers of nephrotoxic acute kidney injury or preventive, or therapeutic targets in sepsis and/or acute kidney injury.	7 days