Initial Resuscitation for Acute Kidney Injury in Cirrhosis

NCT06525623 | Recruiting DMC

• 2 other identifiers: 2024P001520K23DK128567
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cirrhosis, Liver; Acute Kidney Injury; Hepatorenal Syndrome

Outcome Measures

Primary Outcomes (3)

• IV albumin received (grams)

  From date of randomization up to 48 hours

• Adherence to suggested guidance

  For the VAGA group, adherence is defined as: No further resuscitation (\<500 mL total volume of IV fluid given), Resuscitation with crystalloid (\>500 mL total IV fluid given, with \<50 g IV albumin and ≤2 units blood), Resuscitation with colloid (≥50 g IV albumin or ≥2 units blood given). For the Standard of Care group, adherence is defined as receiving within 20% of the suggested IV albumin dose in grams.

  From date of randomization up to 48 hours

• Incidence of treatment-emergent adverse events and serious adverse events

  From date of randomization up to hospital discharge, assessed up to 90 days

Secondary Outcomes (5)

• IV albumin received (grams)

  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

  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

  From date of randomization up to 90 days

• Renal Replacement Therapy Initiation

  From date of randomization up to 90 days

• Liver transplant

  From date of randomization up to 90 days

Study Arms (2)

VAGA Group

EXPERIMENTAL

This group will receive an algorithm-based recommendation based on the 2024 Acute Disease Quality Initiative (ADQI)/International Club of Ascites (ICA) joint consensus meeting on AKI in cirrhosis, which recommends a personalized approach to AKI in cirrhosis in order to avoid volume overload. This includes balanced crystalloids as first-line resuscitative fluids unless there is a patient-specific indication for an alternative colloid (e.g. blood for gastrointestinal bleeding, IV albumin for spontaneous bacterial peritonitis or suspicion of hepatorenal syndrome), or no further resuscitation.

Other: Recommendation: No Further Resuscitation; Other: Recommendation: Resuscitation with Crystalloid; Other: Recommendation: Resuscitation with Colloid

Standard of Care

PLACEBO COMPARATOR

This group will receive a recommendation based on the 2021 American Association for the Study of Liver Diseases (AASLD) and 2018 European Association for the Study of the Liver (EASL) clinical practice guidelines, which recommends a 1 g/kg/d IV albumin (maximum 100 g/day) IV albumin over 2 days as an initial resuscitation approach for patients with AKI and cirrhosis.

Other: Recommendation: Standard of Care IV Albumin

Interventions

Recommendation: Resuscitation with Crystalloid OTHER

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

VAGA Group

Recommendation: Resuscitation with Colloid OTHER

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

VAGA Group

Recommendation: Standard of Care IV Albumin OTHER

Treatment teams are encouraged to administer 1 g/kg/d IV albumin (maximum 100 g/day) over 2 days

Standard of Care

Recommendation: No Further Resuscitation OTHER

Treatment teams are encouraged not to administer any additional fluids

VAGA Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol. 2024 Jul;81(1):163-183. doi: 10.1016/j.jhep.2024.03.031. Epub 2024 Mar 26.

  PMID: 38527522 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Acute Kidney Injury; Hepatorenal Syndrome

Interventions

Crystalloid Solutions; Colloids

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Isotonic Solutions; Solutions; Pharmaceutical Preparations; Complex Mixtures; Dosage Forms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Critical Care Nephrology

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 29, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: After the final research data set has been accepted for publication for 1 year.
• Access Criteria: Upon request

Locations

US (1)