Liberation From Acute Dialysis (LIBERATE-D)

LIBERation From AcuTE Dialysis

The goal of the LIBERATE-D clinical trial is to improve outcomes for patients recovering from dialysis-requiring acute kidney injury (AKI-D). The impact of a conservative dialysis strategy compared to standard clinical practice of thrice-weekly dialysis will be examined to help generate knowledge for how to guide delivery of dialysis to facilitate renal recovery.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Dialysis Related Complication; Kidney; Disease, Acute
• Intervention / Treatment: Procedure: Dialysis

Detailed Description

Dialysis-requiring acute kidney injury (AKI-D) is a devastating complication among hospitalized patients for which there are no treatments other than supportive care. Recovery of sufficient renal function to stop dialysis is an unequivocally important clinical and patient-oriented outcome. Shortening dialysis duration and increasing the number of AKI-D patients who recover would have a major clinical, public health and cost-saving impact. However, there is currently no evidence to guide the delivery of dialysis to facilitate recovery. The investigators hypothesize that in patients who have AKI-D and who are hemodynamically stable, a conservative dialysis strategy--in which hemodialysis is not continued unless specific metabolic or clinical indications for renal replacement therapy (RRT) are present--will improve the likelihood of renal recovery compared with the current standard clinical practice of thrice-weekly intermittent dialysis. The investigators have conducted a pilot clinical trial to demonstrate the feasibility of this approach. The investigators propose here a 2-center randomized controlled trial to test a conservative dialysis strategy in a larger AKI-D population (N = 220).

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kathleen Liu, MD, PhD, MAS; Phone Number: 4155027998; Email: kathleen.liu@ucsf.edu
• Study Contact Backup: Name: Chi-yuan Hsu, MD, MSc; Phone Number: 4153532379; Email: chi-yuan.hsu@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of Califonia, San Francisco
      • Contact: Kathleen Liu, MD, PhD, MAS; Phone Number: 415-502-7998; Email: kathleen.liu@ucsf.edu
      • Contact: Chi-yuan Hsu, MD, MSc; Phone Number: 415-353-2379; Email: chi-yuan.hsu@ucsf.edu
      • Principal Investigator: Kathleen Liu, MD, PhD, MAS
      • Principal Investigator: Chi-yuan Hsu, MD, MSc
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Active, not recruiting
      • Washington University in St Louis/Barnes-Jewish Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Edward Siew, MD; Phone Number: 615-343-1279; Email: edward.siew@vumc.edu
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Medical Center
      • Contact: Anitha Vijayan, MD; Phone Number: 385-630-5660

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age
• Inpatient with AKI-D (intermittent hemodialysis or continuous renal replacement therapy received on at least one calendar day) at least partially due t acute tubular necrosis per the clinical nephrology team
• Hemodynamic stability: not requiring vasopressor support and with planned intermittent dialysis
• Baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2

Exclusion Criteria:

• Nontraditional indication for dialysis (end-stage liver disease awaiting transplantation, fulminant hepatic failure, intoxication)
• Complete nephrectomy as cause of AKI-D
• Kidney transplant during index hospitalization
• Dialysis > 3 months
• Decompensated heart failure requiring left ventricular assist device or continuous inotropic support
• Mechanical ventilation via endotracheal tube
• Hypoxemia requiring significant oxygen support: >5 liters/min via nasal cannula or equivalent via face mask/tracheostomy mask to maintain oxygen saturation > 95%, or requiring fraction of inspired oxygen >50% in patients with tracheostomy requiring invasive or non-invasive ventilation
• Unable to consent and no surrogate decisionmaker available
• Pregnant
• Prisoner
• Clinical team declines to allow study participation
• Anticipated discharge or transfer from study hospital within 48 hours

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
Active Comparator: Conventional; Thrice-weekly intermittent dialysis until pre-specified criteria for recovery are met	Procedure: Dialysis; Dialysis treatment, either in the form of hemodialysis or continuous renal replacement therapy (if patient develops hemodynamic instability)
Experimental: Conservative; Conservative dialysis strategy--dialysis prescribed only when specific metabolic or clinical indications are met. These indications are: blood urea nitrogen >112 mg/dL (40 mmol/L; blood potassium concentration >6 mmol/L; blood potassium concentration >5.5 mmol/L despite medical treatment; arterial blood gas pH <7.15, or in the absence of an available blood gas, serum bicarbonate <12 mmol/L, acute pulmonary edema due to fluid overload, responsible for hypoxemia requiring oxygen flow rate >5 L/min or equivalent via face mask/tracheostomy mask to maintain SpO2 >95% or requiring FiO2 >50% in patients with tracheostomy already on invasive or non-invasive mechanical ventilation and despite diuretic therapy; clinician judgement	Procedure: Dialysis; Dialysis treatment, either in the form of hemodialysis or continuous renal replacement therapy (if patient develops hemodynamic instability)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with renal recovery at hospital discharge	Alive and off dialysis at the time of discharge, with sustained independence from dialysis for 14 days. This outcome does not require that all 14 days of sustained independence occur in-hospital.	Up to 14 days after hospital discharge (to allow for ascertainment of outcome at hospital discharge, which requires a period of sustained dialysis independence)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of dialysis sessions/week	Number of dialysis sessions prescribed in each treatment arm, expressed per week.	Up to 28 days
Dialysis-free days to study day 28	The number of days that a patient did not need dialysis to study day 28. A patient can only accrue dialysis-free days after the final dialysis session that commences the monitoring period for renal recovery. Subjects who die before study day 28 will be considered to have zero dialysis-free days.	Up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal recovery at day 28	Alive and off dialysis at day 28, with sustained independence from dialysis for 14 days.	Up to 42 days (to allow for ascertainment of outcome at day 28, which requires a period of sustained dialysis independence)
Renal recovery	Alive and off dialysis at day 90, with sustained independence from dialysis for 14 days.	Up to 104 days (to allow for ascertainment of outcome at day 28, which requires a period of sustained dialysis independence)
All-cause in-hospital mortality	Vital status at the time of hospital discharge	Up to date of death from any cause, assessed up to 12 months
All-cause day 28 mortality	Vital status at day 28 after study enrollment	Up to 28 days
All-cause day 90 mortality	Vital status at day 90 after study enrollment	Up to 90 days
Length of hospital stay	Duration of hospital stay after study enrollment	Up to date of hospital discharge or death from any cause, whichever comes first, assessed up to 12 months
Time to renal recovery	Days after study enrollment before renal recovery occurs	Up to day 90
Pre-specified adverse events	Adverse events that might be related to the dialysis intervention, including emergent dialysis sessions, intradialytic hypotension and post-dialysis hypotension	Up to 28 days

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH); Vanderbilt University Medical Center
• Investigators: Principal Investigator: Kathleen Liu, MD, PhD, MAS, University of California, San Francisco; Principal Investigator: Chi-yuan Hsu, MD, MSc, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury; Acute Disease
• Other Study ID Numbers: LIBERATED; R01DK122797 (U.S. NIH Grant/Contract)

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