Resuscitation Methods for Acute Kidney Injury in Liver Cirrhosis

(RAKI-VAGA Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Oxygen, Shock, Allergy, Encephalopathy, others

Compensation: Varies

Number of Visits: 92

Duration: 2 days

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, certain medications like vasoconstrictors for AKI treatment are allowed, so it's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment for resuscitation in acute kidney injury in liver cirrhosis?

Research suggests that albumin infusion may be beneficial for patients with liver cirrhosis, especially in conditions like large-volume paracentesis and hepatorenal syndrome, due to its clinical benefits shown in trials. Additionally, albumin has been found to be superior to saline in certain settings, and its use is recommended when other resuscitation methods have been exhausted. ^{1 2 3 4 5}

Is the use of albumin and crystalloids safe for resuscitation in humans?

The use of albumin for resuscitation is generally considered safe in humans, as shown in the SAFE study, except in cases of traumatic brain injury where it may increase mortality. Crystalloids are also widely used and considered safe, but they do not offer a survival benefit over colloids like albumin in critically ill patients. ^{1 2 3 4 6}

How does the treatment for acute kidney injury in liver cirrhosis differ from other treatments?

This treatment is unique because it uses intravenous albumin, which is a protein solution, to help manage fluid balance and improve blood pressure in patients with liver cirrhosis and acute kidney injury. Albumin is preferred over other fluids like saline due to its ability to better maintain blood volume and pressure, especially in patients with liver-related complications. ^{1 2 4 5 7}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for patients with liver cirrhosis who have developed acute kidney injury. Participants should not be receiving any other treatments that could affect the study results, and they must be able to follow the trial procedures.

Inclusion Criteria

I have been diagnosed with advanced liver disease.

I am currently admitted to a hospital.

I have signed the consent form myself, or my legal representative has.

Exclusion Criteria

I have received more than 200 grams of albumin during my current hospital stay.

I needed 3 or more blood transfusions due to severe bleeding in the last 2 days.

Pregnant or nursing status

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a VAGA-based recommendation or standard of care IV albumin for volume resuscitation

2 days

1 visit (in-person)

Initial Follow-up

Participants are assessed for primary efficacy and feasibility outcomes, including grams of albumin and adherence to guidance

48 hours

1 visit (in-person)

Extended Follow-up

Participants are monitored for safety and efficacy outcomes, including AKI response, vital status, and liver transplant status

Up to 90 days

Assessments at hospital discharge and 90 days post-randomization

Treatment Details

Interventions

• Recommendation: Resuscitation with Crystalloid
• Recommendation: Standard of Care IV Albumin

Trial Overview The study compares two methods of giving IV fluids in cirrhosis patients with acute kidney injury: a Volume Assessment Guidance Algorithm (VAGA) recommendation versus standard care with IV albumin. Patients are randomly assigned to one of these approaches.

Participant Groups

Group I: VAGA Group Experimental Treatment 3 Interventions

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.

Group II: Standard of Care Placebo Group 1 Intervention

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.

Recommendation: Resuscitation with Crystalloid is already approved in United States, European Union for the following indications:

Approved in United States as Crystalloid Resuscitation for:

• Acute Kidney Injury in Cirrhosis
• Hypovolemia
• Shock

Approved in European Union as Crystalloid Resuscitation for:

• Acute Kidney Injury
• Cirrhosis-related complications
• Fluid resuscitation

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Patients with decompensated cirrhosis have unique physiological changes that affect how they should be resuscitated, highlighting the need for tailored approaches to minimize complications.

Current evidence suggests that albumin may be more effective than saline for resuscitation in these patients, particularly in procedures like large-volume paracentesis, but more research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decompensated Cirrhosis and Fluid Resuscitation. Maynard, E.[2017]

In critically ill patients with cirrhosis and sepsis-induced hypotension, 20% albumin was more effective than plasmalyte in achieving a mean arterial pressure above 65 mmHg within 3 hours, with 62% of patients responding compared to only 22% with plasmalyte (p < 0.001).

Despite the faster improvement in hemodynamics and lactate clearance with 20% albumin, there was no significant difference in 28-day mortality rates between the two groups, and 20% albumin was associated with more pulmonary complications, indicating that plasmalyte may be a safer option for volume resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]. Maiwall, R., Kumar, A., Pasupuleti, SSR., et al.[2022]

Recent meta-analyses indicate that colloid solutions do not provide a survival advantage over crystalloid solutions for critically ill patients, suggesting that crystalloids may be the preferred choice for volume resuscitation.

Albumin may be beneficial specifically for patients with cirrhosis or those at high risk of acute renal failure, highlighting the need for further research to determine the best fluid composition for resuscitation in shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crystalloids versus colloids for resuscitation in shock. Waikar, SS., Chertow, GM.[2019]

The SAFE study indicates that using albumin for volume therapy is generally safe, although hypo-oncotic albumin should be avoided in cases of traumatic brain injury.

Albumin is recommended for specific conditions like liver cirrhosis and large-volume paracentesis due to proven clinical benefits, but more research is needed to establish its efficacy in broader applications, such as septic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of albumin : State of the art]. Mayerhöfer, T., Wiedermann, CJ., Joannidis, M.[2021]

In a study of 2265 septic patients with liver cirrhosis, daily albumin infusion was linked to a 24% reduction in the risk of 28-day mortality, suggesting it is an effective treatment strategy.

The most significant benefits from albumin infusion were observed when treatment was initiated under specific conditions, such as low serum albumin levels (2.5-3.0 g/dL), high serum lactate (≥2 mmol/L), low mean arterial pressure (<60 mmHg), or moderate vasopressor use (0.2-0.3 mcg/kg/min).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of indications for albumin administration in septic patients with liver cirrhosis. Hu, W., Chen, H., Ma, C., et al.[2023]

A large-scale study (SAFE) found that albumin and saline are equally effective for volume resuscitation in critically ill patients, but albumin is linked to higher mortality in patients with traumatic brain injury, making it unsuitable for their acute treatment.

While albumin is generally safe and effective for resuscitation in critically ill patients without traumatic brain injury, its high cost and lack of proven benefits over cheaper crystalloids like saline raise questions about its routine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin is a blood product too - is it safe for all patients? Myburgh, JA., Finfer, S.[2015]

In a study of 6,786 hospitalized cirrhotic patients with acute kidney injury (AKI), only 35% received intravenous albumin, and its use was not linked to improved recovery from AKI or in-hospital survival.

Despite guidelines recommending albumin for AKI in cirrhosis, the findings suggest that its administration did not lead to better outcomes, highlighting the need for further randomized trials to assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice patterns and outcomes associated with intravenous albumin in patients with cirrhosis and acute kidney injury. Patidar, KR., Adibuzzaman, M., Naved, MA., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Decompensated Cirrhosis and Fluid Resuscitation. [2017]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Crystalloids versus colloids for resuscitation in shock. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

[Use of albumin : State of the art]. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Identification of indications for albumin administration in septic patients with liver cirrhosis. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Albumin is a blood product too - is it safe for all patients? [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Practice patterns and outcomes associated with intravenous albumin in patients with cirrhosis and acute kidney injury. [2022]