Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06556472
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-30
Brief Title:
Safety and Efficacy of Continuous Infusion of Terlipressin With Norepinephrine Versus Norepinephrine Alone in Improving Outcomes of Acute Kidney Injury in Acute on Chronic Liver Failure With Septic Shock
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Safety and Efficacy of Continuous Infusion of Terlipressin With Norepinephrine Versus Norepinephrine Alone in Improving Outcomes of Acute Kidney Injury in Acute on Chronic Liver Failure With Septic Shock - A Randomised Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
ACLF is defined differently in APASLEASL and AASLDAPASL talks of reversibility in ACLF as per its definition and constitution of Homogenous population with ACLFThe definition of ACLF as per APASL is an acute hepatic insult manifesting as jaundice serum bilirubin 5 mgdL 85 micromolL and coagulopathy INR 15 or prothrombin activity 40 complicated within 4 weeks by clinical ascites andor encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver diseasecirrhosis and is associated with a high 28-day mortality
At the onset of septic shock there is initially an increased secretion of Arginine vasopressin However this initial rise is short lasting and the vasopressin levels come back to normal or low serum levels with continued hypotension However even normal levels are too low for the degree of hypotension in septic shock This causes a relative deficiency of vasopressin in septic shock The exact time when this fall happens is not known and it is likely to be variable Vasopressin was therefore tried as an agent in septic shock Terlipressin is a synthetic analogue of vasopressin It has a greater selectivity for the V1 receptor
Currently Norepinephrine is recommended as the first vasopressor to be started in general in septic shock population3 Catecholamines are the clinically used vasopressor agents of choice for supporting arterial blood pressure and ensuring adequate organ perfusion
Development of adrenergic hyposensitivity with loss of catecholamine presser effects is seen in advanced stages of Vasodilatory Shock Progressively increasing catecholamine therapy frequently enters into a vicious cycle of major adverse side effects resulting in continuous clinical deterioration necessitating further catecholamine excess
At the onset of septic shock there is initially an increased secretion of Arginine vasopressin However this initial rise is short lasting and the vasopressin levels come back to normal or low serum levels with continued hypotension However even normal levels are too low for the degree of hypotension in septic shock This causes a relative deficiency of vasopressin in septic shock The exact time when this fall happens is not known and it is likely to be variable Vasopressin was therefore tried as an agent in septic shock Terlipressin is a synthetic analogue of vasopressin It has a greater selectivity for the V1 receptor
Currently Norepinephrine is recommended as the first vasopressor to be started in general in septic shock population3 Catecholamines are the clinically used vasopressor agents of choice for supporting arterial blood pressure and ensuring adequate organ perfusion
Development of adrenergic hyposensitivity with loss of catecholamine presser effects is seen in advanced stages of Vasodilatory Shock Progressively increasing catecholamine therapy frequently enters into a vicious cycle of major adverse side effects resulting in continuous clinical deterioration necessitating further catecholamine excess
Detailed Description:
Aim To study the safety and efficacy of low-dose continuous infusion of terlipressin with norepinephrine compared to norepinephrine alone in improving outcomes of Acute kidney injury occurring in the context of septic shock in patients with Acute on chronic liver failure
Study population
1 septic shock with AKI in patients of ACLF
Study design Prospective open labelled randomised controlled study The study will be conducted in Department of Hepatology ILBS- intensive care unit
At admission
Complete history and physical examination
- Recent Diuretics use
- Loose stools Recurrent vomiting
Fever signs of sepsis Systemic inflammatory response syndrome shock respiratory tract infectionspontaneous bacterial peritonitis
Recent contrast use 7 days nephrotoxins use including NSAIDs
Prior renal dysfunction chronic kudney disease history of Hemodialysis
History of Hypertension Diabetes renal stones
Baseline workup for Acute on chronic liver failure
Severity of liver diseaseAARC-ACLF MELD score CTP score B Intervention during 0-3 hours Before randomization - Pre-randomization interventions
Withdrawal of diuretics Withdrawal of lactulose in patients with loose stools
IV hydration with 5 albumin according to FRISC protocol
Urine output monitoring catheterize and monitor hourly hourly MAP Pulse rate
Use of broad-spectrum IV antibiotics promptly within the first hour in case of suspectedproven sepsis Avoid nephrotoxic drugs as possible
Lung ultrasound and IVC Inferior Vena Cava measurements will be performed at baseline and hourly for 3 hours
Fluid boluses will be administered based on IVC measurements and lung ultrasound findings
Fluid bolus criteria include IVCCIinferior vena cava collapsibility index 40 and an A profile on lung ultrasound
The stopping rule for fluid boluses is IVCCI 40 or a B profile on lung ultrasound
Patients showing improvement within 3 hours will be excluded from further intervention
Monitoring Hemodynamic- MAPHR Urine output hourly
Metabolic - lactate blood sugar electrolytes
Microbiologic - urine -routine microscopy and culture ascitic fluid analysis along with gram stain and cs in blood culture bottle sputum or mini BAL -Cs Gram stain Daily
Others - daily chest X-ray Procalcitonin Cardiac-ECG 2D echo Prognostic models CTP MELD SOFA daily
Stopping Rule
Requirement of Third Vasopressor Need of Norepinephrine 05 mcgkgmin
If a patient requires norepinephrine at a dose exceeding 05 mcgmin indicating the need for a third vasopressor this criterion triggers specific actions as per the study protocol
Threshold Stopping Rule for Fluid Boluses
Fluid boluses will be administered based on IVC and lung ultrasound findings
The stopping rule for fluid boluses is activated if any of the following criteria are met
IVC 25
IVCCI 40
B profile on lung ultrasound
Severe Side Effects or Toxicities CTAE Grade 4
If a patient experiences severe side effects or toxicities categorized as CTAE Common Terminology Criteria for Adverse Events Grade 4 including arrhythmia AMI Acute Myocardial Infarction cardiomyopathy as defined later cyanosis suspicion or confirmed bowel ischemia or any other severe adverse event specific actions or interventions may be required
Salvage group Patient Unwilling for Further Hospital Stay Non responders or when patient in either arm failed
Study will be stopped and management will be done accordingly to guidelines
Adverse effects to terlipressin
Further increase in MAP to be maintained by addition of other vasopressors--vasopressin phenylephrinesteroids
If the target MAP is not achieved in arm A a third vasopressor along with hydrocortisone Adrenaline and then phenylephrine
If the target MAP is not achieved in arm B vasopressin along with hydrocortisone followed by adrenaline and phenylephrine may be added as a fourth vasopressor
The indication for start of steroid
Maximum dose of vasopressor in each arm and all patients in salvage arm
Hydrocortisone 100-150mg bolus start followed by 50mg q6hrly and later tapering dose
Study population
1 septic shock with AKI in patients of ACLF
Study design Prospective open labelled randomised controlled study The study will be conducted in Department of Hepatology ILBS- intensive care unit
At admission
Complete history and physical examination
- Recent Diuretics use
- Loose stools Recurrent vomiting
Fever signs of sepsis Systemic inflammatory response syndrome shock respiratory tract infectionspontaneous bacterial peritonitis
Recent contrast use 7 days nephrotoxins use including NSAIDs
Prior renal dysfunction chronic kudney disease history of Hemodialysis
History of Hypertension Diabetes renal stones
Baseline workup for Acute on chronic liver failure
Severity of liver diseaseAARC-ACLF MELD score CTP score B Intervention during 0-3 hours Before randomization - Pre-randomization interventions
Withdrawal of diuretics Withdrawal of lactulose in patients with loose stools
IV hydration with 5 albumin according to FRISC protocol
Urine output monitoring catheterize and monitor hourly hourly MAP Pulse rate
Use of broad-spectrum IV antibiotics promptly within the first hour in case of suspectedproven sepsis Avoid nephrotoxic drugs as possible
Lung ultrasound and IVC Inferior Vena Cava measurements will be performed at baseline and hourly for 3 hours
Fluid boluses will be administered based on IVC measurements and lung ultrasound findings
Fluid bolus criteria include IVCCIinferior vena cava collapsibility index 40 and an A profile on lung ultrasound
The stopping rule for fluid boluses is IVCCI 40 or a B profile on lung ultrasound
Patients showing improvement within 3 hours will be excluded from further intervention
Monitoring Hemodynamic- MAPHR Urine output hourly
Metabolic - lactate blood sugar electrolytes
Microbiologic - urine -routine microscopy and culture ascitic fluid analysis along with gram stain and cs in blood culture bottle sputum or mini BAL -Cs Gram stain Daily
Others - daily chest X-ray Procalcitonin Cardiac-ECG 2D echo Prognostic models CTP MELD SOFA daily
Stopping Rule
Requirement of Third Vasopressor Need of Norepinephrine 05 mcgkgmin
If a patient requires norepinephrine at a dose exceeding 05 mcgmin indicating the need for a third vasopressor this criterion triggers specific actions as per the study protocol
Threshold Stopping Rule for Fluid Boluses
Fluid boluses will be administered based on IVC and lung ultrasound findings
The stopping rule for fluid boluses is activated if any of the following criteria are met
IVC 25
IVCCI 40
B profile on lung ultrasound
Severe Side Effects or Toxicities CTAE Grade 4
If a patient experiences severe side effects or toxicities categorized as CTAE Common Terminology Criteria for Adverse Events Grade 4 including arrhythmia AMI Acute Myocardial Infarction cardiomyopathy as defined later cyanosis suspicion or confirmed bowel ischemia or any other severe adverse event specific actions or interventions may be required
Salvage group Patient Unwilling for Further Hospital Stay Non responders or when patient in either arm failed
Study will be stopped and management will be done accordingly to guidelines
Adverse effects to terlipressin
Further increase in MAP to be maintained by addition of other vasopressors--vasopressin phenylephrinesteroids
If the target MAP is not achieved in arm A a third vasopressor along with hydrocortisone Adrenaline and then phenylephrine
If the target MAP is not achieved in arm B vasopressin along with hydrocortisone followed by adrenaline and phenylephrine may be added as a fourth vasopressor
The indication for start of steroid
Maximum dose of vasopressor in each arm and all patients in salvage arm
Hydrocortisone 100-150mg bolus start followed by 50mg q6hrly and later tapering dose
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