Clinical trial NCT06525623: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cirrhosis, Liver
Acute Kidney Injury
Hepatorenal Syndrome
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2024-07-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Adult age 18 years or greater
2. 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.
3. Admitted to the hospital
4. Diagnosis of decompensated cirrhosis (either prior to admission or new diagnosis on admission).
5. 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:

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

Primary outcomes:
measure: IV albumin received (grams)
timeFrame: From date of randomization up to 48 hours
measure: Adherence to suggested guidance
timeFrame: From date of randomization up to 48 hours
measure: Incidence of treatment-emergent adverse events and serious adverse events
timeFrame: From date of randomization up to hospital discharge, assessed up to 90 days
Secondary outcomes:
measure: IV albumin received (grams)
timeFrame: 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.
measure: AKI Response
timeFrame: 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.
measure: Vital Status
timeFrame: From date of randomization up to 90 days
measure: Renal Replacement Therapy Initiation
timeFrame: From date of randomization up to 90 days
measure: Liver transplant
timeFrame: From date of randomization up to 90 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.