Study to Evaluate the Efficacy of Intravenous Administration of Human Albumin Versus Saline Solution in Patients With descompénsate Cirrhosis Grade 1B or Higher Renal Failure

Official title

LIVER AKI: A Randomized, Open-label Trial to Evaluate the Efficacy of Intravenous Human Albumin Administration Versus Saline Solution (NaCl 0.9%) in Patients With descompénsate Cirrhosis and AKI 1B or Grater

Overview

This is a phase IV, unicentric, open-label. Patients eligible for this study will be patients with AKI 1B or greater and decompensated cirrhosis from the hospital participating in the study

Detailed description

This is a phase IV, unicentric, open-label, randomized clinical trial to evaluate the efficacy of intravenous human albumin administration versus saline solution (NaCl 0.9%) in patients with decompensated cirrhosis and AKI 1B or grater.

Patients will be randomized to receive (1:1):

1. Intravenous Human Albumin 20% (20 g/100 ml), at a dose of 1 g per kg body weight with a maximum of 100 g per day, during 48 hours. 2. Saline solution (NaCl 0.9%) 500 ml every 24 hours, administered during 48 hours. Patients will be followed up for 28 days since the administration of the treatment (at baseline visit).

Interventions

• Drug Saline solution (NaCl 0.9%)
  Saline solution (NaCl 0.9%) 500 ml every 24 hours, administered during 48 hours.

Primary outcome measures

• probability of AKI resolution among patients with decompensated cirrhosis and AKI 1B or greater acute kidney injury (AKI) clinical efficacy of HA versus saline (NaCl 0.9%) administration in patients will be evaluated, [Time frame: at any time during the study (all visits: screenning, basal , day 1, day2, day 5, day 7, day 15, and day 28)]

Secondary outcome measures (10)

• Survival rate patients [Time frame: at 28 days (visit 6)]
• AKI improvement [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Proportion of patients requiring RRT In both groups [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Changes from baseline in systemic inflammatory response, evaluated by measurement in a large array of plasma cytokine levels (IL-6, IL8, IL-10, IL-1β) [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Changes from baseline in systemic inflammatory response, evaluated by measurement in TNFα, [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Changes from baseline inG-CSF [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma copeptin [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28),]
• Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma renin concentration [Time frame: basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]
• Changes in echocardiographic parameters (E/E', ITV, among others) at visit 1, 2, 7 and 28. [Time frame: basal visit , day 1, day2, day 7, day, and day 28)]
• Proportion of patients and severity of treatment-related adverse events during the study period [Time frame: screening visit,basal visit , day 1, day2, day 5, day 7, day 15, and day 28)]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old.
• Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. (Cirrhosis of any etiology may be included).
• Patients with AKI 1B or greater, defined according to EASL guidelines (EASL. J Hepatol 2018).
• Women of child-bearing potential\* must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence\*\* (only if refraining from heterosexual intercourse during the period of twelve months). Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function

Exclusion criteria

• Time since AKI diagnosis > 24 hours.
• Patients with AKI due to pure hypovolemia. According to guidelines, these patients should receive crystalloid solutions (i.e. NaCl 0.9%) and will be excluded from the study. Fluid losses will be specifically assessed by an accurate anamnesis and physical examination. If patient's diuretic treatment has been increased recently (within prior 2 weeks), or the patient had diarrhea before admission, patient will be considered that the AKI phenotype is pre-renal and will be excluded from the analysis. Patients will be excluded when clear evidence of hypovolemia is present, based on clinical history (e.g, recent fluid losses, diuretic escalation, diarrhea) and corroborating physical findings (e.g, dry mucous membranes, reduced skin turgor, sunken eyes, or low jugular venous pressure)
• Patients with AKI due to gastrointestinal bleeding with AKI 1B or greater, and hemoglobin < 7.0 g/dL. These patients can be included after 48 hours without rebleeding and Hb ≥ 8.0 g/dL, and still present AKI 1B or greater.
• Patients who had already received albumin at the time of inclusion/exclusion criteria assessment.
• Patients with Chronic kidney disease grade 3a or higher, defined as glomerular filtration rate <60ml/min for three months and markers of kidney damage (one or more): Albuminuria (Albumin excretion rate > 30 mg/24h; Albumin-to-creatinine ratio > 30 mg/g), Urine sediment abnormalities, Electrolyte and other abnormalities due to tubular disorders, Abnormalities detected by histology or Structural abnormalities detected by imaging.
• Patients under renal replacement therapy, or with urgent criteria of RRT.
• Patients with hepatocellular carcinoma beyond Milan criteria.
• Patients with severe extrahepatic comorbidities, including congestive heart failure New York Heart Association Grade III/IV, chronic obstructive pulmonary disease Global Initiative for Chronic Obstructive Lung Disease group 2 or higher.
• Previous liver and/or kidney transplantation.
• Patients with current extra hepatic malignancies including solid tumors and hematologic disorders.
• Patients included in other clinical trials in the month before inclusion.
• Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
• Refusal to give informed consent.

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07270874 · LIVER-AKI

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗