SepsisNCT04991376
Specific miRNAs in Sepsis and Nephrotoxic Antibiotic Treatment
An observational study of Sepsis and Septic Shock, run by University Hospital Ostrava at 1 site in Czechia.
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). Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Sepsis, Septic Shock, Acute Kidney Injury
- What is being tested?
- Blood-specific miRNA levels
- How many people
- 53 participants
- Where
- 1 siteCzechia
- Study dates
- 2 May 2019to 1 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- Adult, Older adult
Study population: Critically ill patients suffering from sepsis and treated with vancomycin, gentamicin, or other antibiotic groups.
Who may be able to join
- Critically ill adult septic patients with or without acute kidney injury treated by antimicrobial therapy
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Czechia1 site
University Hospital Ostrava
Ostrava, Moravian-Silesian Region, 70852
About this study
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
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.
Read the detailed 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.
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury
- Being tested
- Blood-specific miRNA levels
- Keywords
- sepsis, septic shock, acute kidney injury, microRNA, nephrotoxicity, vancomycin, gentamicin
- Medical subject headings
- Sepsis, Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood-specific miRNA levelsDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Vancomycin | Critically ill patients who suffered from sepsis, treated with vancomycin. Receives: Diagnostic Test: Blood-specific miRNA levels | |
| Gentamicin | Critically ill patients who suffered from sepsis, treated with gentamicin. Receives: Diagnostic Test: Blood-specific miRNA levels | |
| Other antibiotic groups | Critically ill patients who suffered from sepsis, treated by other antibiotic groups except for vancomycin or aminoglycoside (gentamicin). Receives: Diagnostic Test: Blood-specific miRNA levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (1)
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.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start2 May 2019
- Primary completion30 Jun 2021
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Ostrava
- Sponsor type
- University, hospital or other
- Collaborators
- Palacky University, University Hospital Olomouc, University of Ostrava, Technical University of Ostrava
- Responsible party
- Sponsor
- Investigators
- Naděžda Petejová, Assoc.Prof.,MD,PhD,MSc, Principal investigator, University Hospital Ostrava
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04991376
- Sponsor's protocol ID
- IK-01-miRNA
- Other IDs
- 01 - RVO - FNOs/2019
- Status last verified
- Dec 2022
- First submitted
- 27 Jul 2021
- Last updated
- 6 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data available to other researchers.
Publications
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.
PubMed 26903338Eckardt 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.
PubMed 19786993Petejova 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.
PubMed 32993185Petejova N, Martinek A, Zadrazil J, Klementa V, Pribylova L, Bris R, Kanova M, Sigutova R, Kacirova I, Svagera Z, Bace E, Stejskal D. Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents. BMC Nephrol. 2022 Mar 19;23(1):111. doi: 10.1186/s12882-022-02726-6.
PubMed 35305556
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04991376
- Acronym / sponsor ID
- IK-01-miRNA
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury
- Keywords
- sepsis, septic shock, acute kidney injury, microRNA, nephrotoxicity, vancomycin, gentamicin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University Hospital OstravaUniversity, hospital or other
- Collaborators
- Palacky University, University Hospital Olomouc, University of Ostrava, Technical University of Ostrava
- Study start
- 2 May 2019 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 5 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vancomycin | – | Diagnostic Test: Blood-specific miRNA levelsCritically ill patients who suffered from sepsis, treated with vancomycin. |
| Gentamicin | – | Diagnostic Test: Blood-specific miRNA levelsCritically ill patients who suffered from sepsis, treated with gentamicin. |
| Other antibiotic groups | – | Diagnostic Test: Blood-specific miRNA levelsCritically ill patients who suffered from sepsis, treated by other antibiotic groups except for vancomycin or aminoglycoside (gentamicin). |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Critically ill patients suffering from sepsis and treated with vancomycin, gentamicin, or other antibiotic groups.
Key inclusion criteria (1 listed)
- Critically ill adult septic patients with or without acute kidney injury treated by antimicrobial therapy
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood-specific miRNA levelsBlood-specific miRNA levels associated with renal tubular damage change in patients treated with vancomycin or gentamicin compared to septic patients treated with other antimicrobials. | Diagnostic test | Gentamicin, Other antibiotic groups, Vancomycin |
Primary outcome
miRNAs expression over 7 days of treatment
Time frame: 7 days
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.
1 secondary outcome
Association between circulating miRNA expression and serum neutrophil gelatinase-associated lipocalin (NGAL) and other renal or inflammatory markers
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2022.
- Background: PubMed 26903338Singer 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.
- Background: PubMed 19786993Eckardt 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.
- Background: PubMed 32993185Petejova 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.
- Derived from this study: PubMed 35305556Petejova N, Martinek A, Zadrazil J, Klementa V, Pribylova L, Bris R, Kanova M, Sigutova R, Kacirova I, Svagera Z, Bace E, Stejskal D. Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents. BMC Nephrol. 2022 Mar 19;23(1):111. doi: 10.1186/s12882-022-02726-6.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naděžda Petejová, Assoc.Prof.,MD,PhD,MSc principal investigator
University Hospital Ostrava
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Septic Shock, run by University Hospital Ostrava at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
miRNAs expression over 7 days of treatment (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04991376, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2022.