Initial Resuscitation for Acute Kidney Injury in Cirrhosis

Official title

Initial Resuscitation for Acute Kidney Injury in Patients With Cirrhosis: A Pilot Randomized Trial Using a Volume Assessment Guidance Algorithm

Overview

The goal of this interventional study is to evaluate two strategies for how to provide intravenous (IV) fluids for treating patients with acute kidney injury (AKI) in cirrhosis. The main question it aims to answer is: what is the safety, efficacy, and feasibility of providing a recommendation to use a Volume Assessment Guidance Algorithm (VAGA) or give standard of care doses of IV albumin? Patients will be randomly assigned where their treating teams will receive a VAGA-based recommendation or a standard of care IV albumin recommendation.

Detailed description

This randomized, open-label, pilot feasibility trial will assess a volume assessment guidance algorithm (VAGA) in patients with AKI and cirrhosis. Eligible patients must have AKI and decompensated cirrhosis. In addition to assessing the adherence to the suggested guidance, this study will measure the effect of the study intervention on grams of albumin given, clinical efficacy outcomes (AKI response rates, survival, RRT status, transplant status), and safety.

Patients who meet eligibility criteria will be randomized 1:1 where the treating clinicians will receive a one-time recommendation for volume resuscitation using the VAGA or standard of care IV albumin repletion (1 g/kg/day for two days). Both groups will be followed with assessments at 48 hours after randomization, hospital discharge, and 90-days after randomization.

The primary efficacy outcome, grams of albumin, will be measured at 48 hours after randomization. Primary secondary efficacy outcomes (grams of albumin, AKI response) will be assessed at time of hospital discharge. If a patient undergoes liver transplantation or initiation of RRT during the admission, this will serve as a censoring date for these outcomes, and relevant data will be collected at the time of the first of these events.

The primary feasibility outcome is adherence to the suggested guidance, assessed at 48 hours after randomization. The VAGA group will receive one of three potential clinical recommendations: (a) no further volume resuscitation, (b) resuscitation with crystalloid, or (c) resuscitation with colloid.

This study will prospectively enroll approximately 50 adult patients at a single center.

Interventions

• Other Recommendation: No Further Resuscitation
  Treatment teams are encouraged not to administer any additional fluids
• Other Recommendation: Resuscitation with Crystalloid
  Treatment teams are encouraged to administer crystalloid. Amount of resuscitative fluid will be determined by treatment team's clinical assessments and usual standards of care
• Other Recommendation: Resuscitation with Colloid
  Treatment teams are encouraged to administer colloid. Amount of resuscitative fluid will be determined by treatment team's clinical assessments and usual standards of care
• Other Recommendation: Standard of Care IV Albumin
  Treatment teams are encouraged to administer 1 g/kg/d IV albumin (maximum 100 g/day) over 2 days

Primary outcome measures

• IV albumin received (grams) [Time frame: From date of randomization up to 48 hours]
• Adherence to suggested guidance [Time frame: From date of randomization up to 48 hours]
• Incidence of treatment-emergent adverse events and serious adverse events [Time frame: From date of randomization up to hospital discharge, assessed up to 90 days]

Secondary outcome measures (5)

• IV albumin received (grams) [Time frame: From date of hospital admission up to hospital discharge, or the date of time of initiation of renal replacement therapy or liver transplant, whichever came first, assessed up to 90 days.]
• AKI Response [Time frame: From date of randomization up to hospital discharge, or the date of time of initiation of renal replacement therapy or liver transplant, whichever came first, assessed up to 90 days.]
• Vital Status [Time frame: From date of randomization up to 90 days]
• Renal Replacement Therapy Initiation [Time frame: From date of randomization up to 90 days]
• Liver transplant [Time frame: From date of randomization up to 90 days]

Eligibility criteria

Inclusion criteria

• Adult age 18 years or greater
• Signed informed consent form (ICF) by any subject capable of giving consent, or, when the subject is not capable of giving consent, by their legally authorized representatives prior to initiation of any study procedures.
• Admitted to the hospital
• Diagnosis of decompensated cirrhosis (either prior to admission or new diagnosis on admission).
• Presence of acute kidney injury (AKI) as defined by International Club of Ascites (ICA) criteria, defined as SCr increase of ≥0.3 mg/dL within 48 hours or ≥50% increase from baseline which is known or presumed to have occurred within the prior 7 days.

Exclusion criteria

• Requiring >2 liters (L) supplemental oxygen at the time of screening.
• In shock requiring vasopressors (vasoconstrictors for the treatment of AKI such as terlipressin, midodrine, and octreotide are allowed).
• Allergy or other contraindication to IV albumin administration.
• Death, liver transplant, or renal replacement therapy (RRT) expected within 48 hours.
• Patient and/or legally authorized representative unable to provide informed consent.
• Hepatic encephalopathy grade 3 or 4 at the time of screening.
• Already received >200 g albumin during admission at the time of screening.
• Severe, active bleeding requiring 3 or more units of red blood cell transfusion in the 48 hours prior to screening.
• Admission to the intensive care unit at the time of screening.
• Mechanical ventilation at the time of screening.
• Presence of New York Heart Association (NYHA) class 3-4 symptoms of congestive heart failure at the time of screening.
• History of prior liver or kidney transplant.
• Pregnant or nursing status
• Any condition, in the opinion of the investigator, that could confound or interfere with the safe completion of study activities.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Massachusetts General Hospital — Boston

Publications

• European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024. Epub 2018 Apr 10. No abstract available. PMID 29653741
• Biggins SW, Angeli P, Garcia-Tsao G, Gines P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug;74(2):1014-1048. doi: 10.1002/hep.31884. No abstract available. PMID 33942342
• Nadim MK, Kellum JA, Forni L, Francoz C, Asrani SK, Ostermann M, Allegretti AS, Neyra JA, Olson JC, Piano S, VanWagner LB, Verna EC, Akcan-Arikan A, Angeli P, Belcher JM, Biggins SW, Deep A, Garcia-Tsao G, Genyk YS, Gines P, Kamath PS, Kane-Gill SL, Kaushik M, Lumlertgul N, Macedo E, Maiwall R, Marciano S, Pichler RH, Ronco C, Tandon P, Velez JQ, Mehta RL, Durand F. Acute kidney injury in patients PMID 38527522

Identifiers

NCT: NCT06525623 · 2024P001520 · K23DK128567

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗