On Demand Versus Protocol-guided Renal Replacement Therapy for Management of Stage 3 Acute Kidney Injury in Patients With Cirrhosis

• ClinicalTrials.gov Identifier: NCT02937935
• Recruitment Status: Unknown
• First Posted: October 19, 2016
• Last Update Posted: November 29, 2017
• Sponsor: Institute of Liver and Biliary Sciences, India
• Information provided by (Responsible Party): Institute of Liver and Biliary Sciences, India

Tracking Information

• First Submitted Date: October 17, 2016
• First Posted Date: October 19, 2016
• Last Update Posted Date: November 29, 2017
• Estimated Study Start Date: July 1, 2018
• Estimated Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 17, 2016): Recovery of renal functions in both groups [ Time Frame: day 14 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 26, 2016)

• Adverse effects of dialysis in the first session in both groups [ Time Frame: 48 hours ]
• Improvement in SOFA (by 2 points) scores in both groups [ Time Frame: 48 hours ]
• Improvement in MELD ( by 2 points) scores in both groups [ Time Frame: 48 hours ]
• Improvement in APACHE ( by 2 points) scores in both groups [ Time Frame: 48 hours ]
• Change to End Stage Renal Disease with requirement of maintenance hemodialysis at least twice a week in both groups [ Time Frame: 4 weeks ]
• Improvement in renal functions in both groups [ Time Frame: 7 days ]
• Mortality in both groups [ Time Frame: 1 month ]
• Mortality in both groups [ Time Frame: 3 month ]
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. [ Time Frame: 6 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. [ Time Frame: 12 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury [ Time Frame: 24 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups [ Time Frame: 24 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.

Original Secondary Outcome Measures (submitted: October 17, 2016)

• Adverse effects of dialysis in the first session in both groups [ Time Frame: 1 year ]
• Improvement in SOFA (by 2 points) scores in both groups [ Time Frame: 1 year ]
• Improvement in MELD ( by 2 points) scores in both groups [ Time Frame: 1 year ]
• Improvement in APACHE ( by 2 points) scores in both groups [ Time Frame: 1 year ]
• Change to End Stage Renal Disease with requirement of maintenance hemodialysis atleast twice a week in both groups [ Time Frame: 4 weeks ]
• Improvement in renal functions in both groups [ Time Frame: 7 days ]
• Mortality in both groups [ Time Frame: 1 month ]
• Mortality in both groups [ Time Frame: 3 month ]
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. [ Time Frame: 6 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups. [ Time Frame: 12 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury [ Time Frame: 24 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.
• Response to vasoconstrictors in patients with Hepatorenal Syndrome-Acute Kidney Injury in both groups [ Time Frame: 24 hours ]
  Response as assessed by either improvement in urine output >0.5ml/kg/hour, acid-base status or renal functions.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: On Demand Versus Protocol-guided Renal Replacement Therapy for Management of Stage 3 Acute Kidney Injury in Patients With Cirrhosis
• Official Title: On Demand Versus Protocol-guided Renal Replacement Therapy for Management of Stage 3 Acute Kidney Injury in Patients With Cirrhosis -A Prospective Randomized Controlled Trial

Brief Summary

Intervention: All patients at presentation would be assessed for the underlying cause of and will be managed by removal of all precipitants(careful review of medications, diuretics, nephrotoxic drugs,vasodilators or non-steroidal anti-inflammatory drugs). The second step would be to consider plasma volume expansion in patients with hypovolemia (the choice of fluid could either be a crystalloid or albumin or even blood as indicated) along with identification and early treatment of bacterial infections. Along with this patients with a differential diagnosis of HRS-AKI would be given terlipressin ( or noradrenaline/octreotide midodrine in case of contraindication to terlipressin). Patients with a clinical diagnosis of ATN would be randomized to the on-demand versus protocol-guided dialysis groups. Further, patients with urine output of less than 0.5ml/kg/hour for 4-6 hours despite adequate fluid resuscitation and vasoconstrictors would also be subjected to randomization.

1. In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization
2. In the protocol guided group patients all patients would be considered for dialysis within 6 hours of randomization After randomization patients would receive dialysis as three sessions per week of at least 4 h with a blood flow >200 mL/min and a dialysate flow >500 mL/min in intermittent group and as 20-25 mL/kg/h of effluent, by filtration and/or diffusion in continuous form until recovery of renal functions

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Kidney Injury With Cirrhosis

Intervention

• Biological: Protocol Guided Renal Replacement Therapy
  In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization.
• Biological: On Demand Renal Replacement Therapy
  Patients to be randomized to the intervention as per standard of care

Study Arms

• Experimental: Protocol Guided-RRT
  In the on-demand group patients would get dialysis only when patient fulfills absolute criteria requiring dialysis such as metabolic acidosis with ph<7.2, hyperkalemia, refractory fluid overload (non-responsive to diuretics) or oliguria with urine output of less than 0.5ml/kg for more than 24-48 hours from the time of randomization.
  Intervention: Biological: Protocol Guided Renal Replacement Therapy
• Active Comparator: On Demand-RRT
  In the protocol guided group patients all patients would be considered for dialysis within 6 hours of randomization After randomization patients would receive dialysis as three sessions per week of at least 4 h with a blood flow >200 mL/min and a dialysate flow >500 mL/min in intermittent group and as 20-25 mL/kg/h of effluent, by filtration and/or diffusion in continuous form until recovery of renal functions
  Intervention: Biological: On Demand Renal Replacement Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 22, 2017): 2
• Original Estimated Enrollment (submitted: October 17, 2016): 150
• Estimated Study Completion Date: July 1, 2019
• Estimated Primary Completion Date: July 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with cirrhosis (diagnosed based on clinical, biochemical,radiological or histological diagnosis) with stage 3 Acute Kidney Injury defined as an increase of serum creatinine to more than 300 fold and more than 4 mg/dl.

Exclusion Criteria:

• Patients with age less than 18 years
• Severe known cardiopulmonary disease (structural or valvular heart disease, coronary artery disease, COPD Chronic Obstructive Pulmonary Disease)
• Pregnancy
• Chronic kidney disease on hemodialysis
• Patients with post renal obstructive AKI (Acute Kidney Injury), AKI (Acute Kidney Injury) suspected due to glomerulonephritis, interstitial nephritis or vasculitis based on clinical history and urine analysis
• Patients already meeting emergency criteria for immediate hemodialysis at the time of randomization (serum potassium>6 meq/lt, metabolic acidosis ph<7.12, acute pulmonary edema, severe volume overload with hypoxemia non-responsive to diuretic treatment)
• Patients transferred from other hospitals who have already been on hemodialysis before their arrival in the intensive care unit
• Extremely moribund patients with an expected life expectancy of less than 24 hours
• Failure to give informed consent from family members.
• Hemodynamic instability requiring very high dose of vasopressors.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India

Administrative Information

• NCT Number: NCT02937935
• Other Study ID Numbers: ILBS-AKI-Cirrhosis
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Institute of Liver and Biliary Sciences, India
• Study Sponsor: Institute of Liver and Biliary Sciences, India
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Institute of Liver and Biliary Sciences, India
• Verification Date: November 2017