Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06646328
Status:
TERMINATED
Last Update Posted:
None
First Post:
2018-07-31
Brief Title:
Oxidative Stress and Circulating Nuclear DNA cfDNA in Acute Kidney Injury and Continuous Renal Replacement Therapies
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Oxidative Stress and Circulating Nuclear DNA cfDNA in Acute Kidney Injury and Continuous Renal Replacement Therapies Effect of Two Anticoagulation Strategies of the Extracorporeal Purification System in Renal Function Recovery
Status:
TERMINATED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Enrollment slower than anticipated and interrupted by COVID-19 pandemic
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Acute kidney injury AKI is the inability of the kidneys to perform their functions of purifying and cleaning the blood It is a frequent complication in hospitalized patients especially in those admitted to the ICUs In these situations is common to use machines to artificially and temporarily replace renal function so waste products that can be toxic are removed from the body
The purpose of this study is to assess the effectiveness and safety of two anticoagulation strategies of the extracorporeal purification system in critically ill patients with acute kidney injury treated with continuous renal replacement therapy CRRT evaluating the effect of both strategies in oxidative stress and extracellular nucleosomes and its influence on the recovery of renal function
The purpose of this study is to assess the effectiveness and safety of two anticoagulation strategies of the extracorporeal purification system in critically ill patients with acute kidney injury treated with continuous renal replacement therapy CRRT evaluating the effect of both strategies in oxidative stress and extracellular nucleosomes and its influence on the recovery of renal function
Detailed Description:
Acute kidney injury AKI is defined as a sudden deterioration of renal function that causes loss of electrolyte control acid base status and fluid balance with subsequent accumulation of nitrogenous waste products that should be eliminated by the kidney It is a frequent complication in hospitalized patients especially those admitted to Intensive Care Units ICUs Its etiology is usually multifactorial usually in the context of multiorgan dysfunction syndrome MODS The epidemiology and risk factors associated with its development as well as the type of treatment that these patients are currently undergoing continues to be the subject of debate given the impact it has on morbidity and mortality
To temporary substitute renal function in critically ill patients continuous renal replacement therapies CRRT are frequently used The classification and nomenclature of techniques depends on the duration continuity and operational characteristics of the treatment system Thus we distinguish between continuous techniques and intermittent techniques Peritoneal dialysis PD is rarely used in developed countries for the treatment of AKI in ICU Intermittent hemodialysis IHD is the most frequently used technique although its use in ICU has considerable limitations on fluid balance uremia control and elimination of medium molecular weight molecules
Due to the enormous difficulty of obtaining studies with the necessary statistical power to provide the degree of evidence needed to clarify questions regarding the indications modalities and other technical aspects of the CRRT it is commonly used the experience that both the clinical practice in chronic patients as the results of scientific research that intermittent techniques IHD fundamentally confers to the clinician
In patients with IHD certain conditions are associated with a worse prognosis and an increased risk of mortality These can include cardiovascular diseases diabetes mellitus DM atherosclerosis infectious processes malnutrition inflammation oxidative stress iron deficiency anemia calcification uremia and volume overload AKI requiring a renal replacement technique RRT represents an independent risk factor for mortality in critically ill patients Oxidative stress and inflammation play important roles in the initiation and extension phases of AKI as well as in causing injury to distant organs after AKI
In CRRT to prevent coagulation of the extracorporeal system requires the use of some method of anticoagulation The most frequent anticoagulation strategies include systemic heparin and regional citrate administration However some undesirable effects of CRRT may affect the patients outcome including the risks of systemic bleeding and membrane biocompatibility induced by anticoagulants
Heparin the most widely used anticoagulant in these techniques is considered the standard of treatment however it is contraindicated in patients with a high hemorrhagic risk or in heparin-induced thrombocytopenia
Regional citrate anticoagulation RCA in which only the extracorporeal circuit is anticoagulated by the chelating action of calcium by citrate is a safe and effective alternative in these cases RCA has also been described as superior to heparin in terms of biocompatibility since heparin in comparison with citrate can activate the complement and induce neutrophil degranulation in the filter and activate the release of myeloperoxidase MPO from the endothelium The use of citrate in addition to providing greater biocompatibility and a similar or longer filter duration could also be associated with less inflammation and possibly with a better survival compared to heparin use and probably also with a better renal recovery
Apoptosis is probably implicated as a pathophysiological mechanism in organ injury in the setting of sepsis and systemic inflammatory response syndrome
The sum effect of the numerous risk factors present in critical patients with AKI treated with CRRT is cumulative additive interrelated complex and often unexpected or completely unknown Survival in patients with AKI requiring replacement therapy is lower than in other patient populations At present the accuracy of prediction of mortality and morbidity depending on available biomarkers or clinical condition is not optimal to properly describe and stratify patients properly The combination of several markers of simultaneous biochemical processes can help to better stratify patients identify the best therapeutic targets evaluate the response to different therapies and establish functional prognoses The usefulness of a parameter that evaluates tissue damage with markers of specific biochemical processes could be considered
The present randomized controlled parallel-group single centre study aims to evaluate the biocompatibility of two strategies of anticoagulation of the extracorporeal system RCA and heparin by using markers of inflammation oxidative stress and cellular damage and its repercussion in the recovery of renal function In this setting it would be possible to establish functional prognoses in terms of renal function recovery and to better identify which strategy is most beneficial for each group of patients
To temporary substitute renal function in critically ill patients continuous renal replacement therapies CRRT are frequently used The classification and nomenclature of techniques depends on the duration continuity and operational characteristics of the treatment system Thus we distinguish between continuous techniques and intermittent techniques Peritoneal dialysis PD is rarely used in developed countries for the treatment of AKI in ICU Intermittent hemodialysis IHD is the most frequently used technique although its use in ICU has considerable limitations on fluid balance uremia control and elimination of medium molecular weight molecules
Due to the enormous difficulty of obtaining studies with the necessary statistical power to provide the degree of evidence needed to clarify questions regarding the indications modalities and other technical aspects of the CRRT it is commonly used the experience that both the clinical practice in chronic patients as the results of scientific research that intermittent techniques IHD fundamentally confers to the clinician
In patients with IHD certain conditions are associated with a worse prognosis and an increased risk of mortality These can include cardiovascular diseases diabetes mellitus DM atherosclerosis infectious processes malnutrition inflammation oxidative stress iron deficiency anemia calcification uremia and volume overload AKI requiring a renal replacement technique RRT represents an independent risk factor for mortality in critically ill patients Oxidative stress and inflammation play important roles in the initiation and extension phases of AKI as well as in causing injury to distant organs after AKI
In CRRT to prevent coagulation of the extracorporeal system requires the use of some method of anticoagulation The most frequent anticoagulation strategies include systemic heparin and regional citrate administration However some undesirable effects of CRRT may affect the patients outcome including the risks of systemic bleeding and membrane biocompatibility induced by anticoagulants
Heparin the most widely used anticoagulant in these techniques is considered the standard of treatment however it is contraindicated in patients with a high hemorrhagic risk or in heparin-induced thrombocytopenia
Regional citrate anticoagulation RCA in which only the extracorporeal circuit is anticoagulated by the chelating action of calcium by citrate is a safe and effective alternative in these cases RCA has also been described as superior to heparin in terms of biocompatibility since heparin in comparison with citrate can activate the complement and induce neutrophil degranulation in the filter and activate the release of myeloperoxidase MPO from the endothelium The use of citrate in addition to providing greater biocompatibility and a similar or longer filter duration could also be associated with less inflammation and possibly with a better survival compared to heparin use and probably also with a better renal recovery
Apoptosis is probably implicated as a pathophysiological mechanism in organ injury in the setting of sepsis and systemic inflammatory response syndrome
The sum effect of the numerous risk factors present in critical patients with AKI treated with CRRT is cumulative additive interrelated complex and often unexpected or completely unknown Survival in patients with AKI requiring replacement therapy is lower than in other patient populations At present the accuracy of prediction of mortality and morbidity depending on available biomarkers or clinical condition is not optimal to properly describe and stratify patients properly The combination of several markers of simultaneous biochemical processes can help to better stratify patients identify the best therapeutic targets evaluate the response to different therapies and establish functional prognoses The usefulness of a parameter that evaluates tissue damage with markers of specific biochemical processes could be considered
The present randomized controlled parallel-group single centre study aims to evaluate the biocompatibility of two strategies of anticoagulation of the extracorporeal system RCA and heparin by using markers of inflammation oxidative stress and cellular damage and its repercussion in the recovery of renal function In this setting it would be possible to establish functional prognoses in terms of renal function recovery and to better identify which strategy is most beneficial for each group of patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None