Liberation From Acute Dialysis (LIBERATE-D)

• ClinicalTrials.gov Identifier: NCT04218370
• Recruitment Status: Recruiting
• First Posted: January 6, 2020
• Last Update Posted: September 29, 2021
• Sponsor: University of California, San Francisco
• Collaborators: Vanderbilt University Medical Center; National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Kidney Injury; Kidney; Disease, Acute; Dialysis Related Complication	Procedure: Dialysis	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LIBERation From AcuTE Dialysis
• Actual Study Start Date: January 23, 2020
• Estimated Primary Completion Date: June 30, 2024
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with renal recovery at hospital discharge [ Time Frame: Up to 14 days after hospital discharge (to allow for ascertainment of outcome at hospital discharge, which requires a period of sustained dialysis independence) ]
   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.

Secondary Outcome Measures :

1. Number of dialysis sessions/week [ Time Frame: Up to 28 days ]
   Number of dialysis sessions prescribed in each treatment arm, expressed per week.
2. Dialysis-free days to study day 28 [ Time Frame: Up to 28 days ]
   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.

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Kathleen Liu, MD, PhD, MAS; 4155027998; kathleen.liu@ucsf.edu

Contact: Chi-yuan Hsu, MD, MSc; 4153532379; chi-yuan.hsu@ucsf.edu

Locations

United States, California

University of Califonia, San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Kathleen Liu, MD, PhD, MAS 415-502-7998 kathleen.liu@ucsf.edu

Contact: Chi-yuan Hsu, MD, MSc 415-353-2379 chi-yuan.hsu@ucsf.edu

Principal Investigator: Kathleen Liu, MD, PhD, MAS

Principal Investigator: Chi-yuan Hsu, MD, MSc

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37212

Contact: Edward Siew, MD 615-343-1279 edward.siew@vumc.edu

Sponsors and Collaborators

University of California, San Francisco

Vanderbilt University Medical Center

National Institutes of Health (NIH)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT04218370
• Other Study ID Numbers: LIBERATED; R01DK122797 ( U.S. NIH Grant/Contract )
• First Posted: January 6, 2020
• Last Update Posted: September 29, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Acute Kidney Injury; Acute Disease; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Disease Attributes; Pathologic Processes