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

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

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

Study Overview

• Status: Unknown
• Conditions: Acute Kidney Injury With Cirrhosis
• Intervention / Treatment: Biological: Protocol Guided Renal Replacement Therapy; Biological: On Demand Renal Replacement Therapy

• Study Type: Interventional
• Enrollment (Anticipated): 2
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Rakhi Maiwall, MD,DM; Phone Number: 01146300000; Email: rakhi_2011@yahoo.co.in

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
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	Biological: On Demand Renal Replacement Therapy; Patients to be randomized to the intervention as per standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recovery of renal functions in both groups	day 14

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 17, 2016
• First Posted (Estimate): October 19, 2016

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: November 28, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Fibrosis; Wounds and Injuries; Liver Cirrhosis; Acute Kidney Injury
• Other Study ID Numbers: ILBS-AKI-Cirrhosis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No