|- candidate number||27055|
|- NTR Number||NTR6303|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-apr-2017|
|- Secondary IDs||2017/077 METC|
|- Public Title||Longterm effects of severe infections and sepsis.|
|- Scientific Title||LONG-term Effects of mitochondrial Vitality in severe InfEctions and Sepsis|
|- hypothesis||Survivors of sepsis are at high risk for the development of chronic kidney disease (CKD), cardiovascular events and mortality. Mitochondrial dysfunction, which mainly results from increased generation of free radicals, plays a key role in the pathogenesis of organ failure during sepsis. While adults are at high risk for acute kidney injury (AKI), elderly are in addition at major risk for acute delirium. Although aging-related damage to mitochondrial DNA (mtDNA) is associated with the development of CKD and (fatal) cardiovascular events, it is not known whether sepsis induces similar changes in mitochondria, which may in turn lead to increased morbidity and mortality after sepsis. |
|- Healt Condition(s) or Problem(s) studied||Mitochondrial dysfunction, Sepsis, Infection|
|- Inclusion criteria||- Adult patients, aged between 18 and 85 years|
- Able to provide (deferred) informed consent themselves or informed consent can be obtained via next of kin or legal guardian
- One or both of the following:
o Clinical suspicion of a pulmonary or urinary tract infection
o Fever (body temperature > 38.5°C)
|- Exclusion criteria||A potential subject who meets any of the following criteria will be excluded from participation in this study:|
- Discharged home without hospital admittance after ED visit
- Congenital mitochondrial diseases
- Renal transplant recipients
- Hepatic failure (Child Pugh C)
- Hepatorenal syndrome
- History of a malignancy other than treated basal cell or squamous cell carcinoma of the skin (those with a history of malignancy that has been treated with no recurrence within the last year are not excluded)
- COPD GOLD IV
- Start of antibiotics before blood sampling
|- mec approval received||no|
|- multicenter trial||no|
|- planned startdate ||1-jun-2017|
|- planned closingdate||1-jun-2020|
|- Target number of participants||100|
|- Interventions||n/a; observational study|
|- Primary outcome||The primary objective of the current project is to study the association between biomarkers for renal mitochondrial damage in sepsis with the change in renal function and mortality after sepsis.|
|- Secondary outcome||The secondary objectives of the current project are: |
- to study the association between biomarkers for renal mitochondrial damage in sepsis with the occurrence of cardiovascular events, co-morbidity, quality of life and functional status after sepsis.
- to study the association between sepsis severity and the induction of renal and systemic mitochondrial damage.
- to study the association between sepsis severity and the induction of renal and systemic DNA damage.
- to study the association between systemic mitochondrial damage in sepsis with (change in) renal function, cardiovascular/renal risk factors, cardiovascular events, co-morbidity, quality of life, health/functional status and mortality after sepsis.
- to study the association between sepsis severity and the (change in) renal function, cardiovascular/renal risk factors, cardiovascular events, co-morbidity, quality of life, functional status and mortality after sepsis.
In addition, the following objectives will be studied in aged individuals (i.e. > 65 years old):
- to study whether delirious patients demonstrate an aberrant functional status and number of circulating immune cells compared to patients that do not develop delirium following sepsis.
- to study the association between peripheral cytokine levels and delirium following sepsis
- to study the association between the occurrence of delirium during sepsis with the occurrence of cardiovascular events, co-morbidity, quality of life, functional status and mortality after sepsis.
|- Timepoints||Inclusion, day 4, 3 months, 1 year, 2 years|
|- Trial web site||www.sepsis.science|
|- CONTACT FOR PUBLIC QUERIES||Dr. H.R. Bouma|
|- CONTACT for SCIENTIFIC QUERIES||Dr. H.R. Bouma|
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|Dutch Kidney Foundation (Nierstichting Nederland)|
|- Brief summary||Mitochondrial dysfunction plays a central role in the pathophysiology of AKI during sepsis, which is in turn associated with increased in-hospital and long-term mortality, as well as an increased risk of CKD among survivors. In this project, we will analyze whether the induction of damage to renal mitochondria during sepsis is associated with a declining renal function, cardiovascular events, co-morbidity, quality of life, functional status and mortality after sepsis.
Although great interindividual variability in ropivacaine concentration was found, both total and unbound maximum serum concentrations remained below the assumed systemic toxic thresholds in all samples.
|- Main changes (audit trail)|
|- RECORD||6-apr-2017 - 25-nov-2018|