AKI - Acute Kidney Injury, Decompensated Cirrhosis
Conditions
Brief summary
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
Saline solution (NaCl 0.9%) 500 ml every 24 hours, administered during 48 hours.
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase IV, unicentric, open-label, randomized clinical trial, low interventional level
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old. 2. Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. (Cirrhosis of any etiology may be included). 3. Patients with AKI 1B or greater, defined according to EASL guidelines (EASL. J Hepatol 2018). 4. 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
1. Time since AKI diagnosis \> 24 hours. 2. 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) 3. 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. 4. Patients who had already received albumin at the time of inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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, | at any time during the study (all visits: screenning, basal , day 1, day2, day 5, day 7, day 15, and day 28) | defining AKI resolution as the proportion of patients with a decrease in serum creatinine levels \< 0.3 mg/dL with respect to baseline serum creatinine, without the need for TRT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival rate patients | at 28 days (visit 6) | Survival rate patients at 28 days, considering liver transplantation as a competitive risk event. |
| AKI improvement | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | defined as the proportion of patients who decrease at least 1 grade of AKI classification (from 3 to 2, from 2 to 1B, and from 1B to 1A or recovery), without the need for RRT. |
| Proportion of patients requiring RRT In both groups | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | Proportion of patients requiring RRT In both groups (renal replacemtent theraphy) |
| Changes from baseline in systemic inflammatory response, evaluated by measurement in TNFα, | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | picograms per mililiter (pg/mL) |
| 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) | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | picograms per mililiter (pg/mL) |
| Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma copeptin | basal visit , day 1, day2, day 5, day 7, day 15, and day 28), | ypically range from 1 to 13 pmol/L |
| Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma renin concentration | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | ng/mL/hr (nanograms per milliliter per hour) |
| Changes in echocardiographic parameters (E/E', ITV, among others) at visit 1, 2, 7 and 28. | basal visit , day 1, day2, day 7, day, and day 28) | (E/E', ITV) |
| Proportion of patients and severity of treatment-related adverse events during the study period | screening visit,basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | number and description SAEs and SUSARs |
| Changes from baseline inG-CSF | basal visit , day 1, day2, day 5, day 7, day 15, and day 28) | micrograms per kilogram of body weight (mcg/kg) |
Contacts
Primary ContactAna CRUCETA, Md
Outcome results
None listed