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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two methods of administering IV fluids to assist individuals with kidney problems caused by liver cirrhosis. One group will receive fluid recommendations based on a special algorithm using crystalloid resuscitation, a type of IV fluid therapy. The other group will follow standard medical guidelines with IV albumin, a protein solution. The trial aims to determine which method is safer, more effective, and easier to use. It may suit hospital patients with both liver cirrhosis and acute kidney injury, a sudden decrease in kidney function. As an unphased trial, this study provides patients the chance to contribute to innovative research that could enhance treatment strategies for complex conditions.

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 prior data suggests that these resuscitation methods are safe for treating acute kidney injury in liver cirrhosis?

Research shows that crystalloid fluids, a type of IV solution, are often used safely in medical settings to restore fluid levels, especially when someone has lost a lot of blood or has low blood volume. Some studies have compared balanced crystalloids to normal saline. These studies found that while balanced crystalloids may not significantly reduce the risk of serious kidney problems, they are generally well-tolerated and do not increase the risk of death.

Conversely, IV albumin is commonly used according to established guidelines for treating sudden kidney problems in patients with liver disease. This treatment is already part of standard medical care, indicating its general safety for conditions like liver cirrhosis.

In summary, both treatments—crystalloid fluids and IV albumin—are used in medical settings and are generally well-tolerated. Crystalloid fluids effectively restore fluid levels, while IV albumin is a trusted standard for managing kidney issues in liver cirrhosis. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these trial methods for acute kidney injury (AKI) in liver cirrhosis because they explore more personalized approaches to resuscitation. Traditionally, the standard of care involves using IV albumin based on guidelines, but the experimental method introduces an algorithm-based recommendation that emphasizes balanced crystalloids and avoids volume overload. This personalized approach allows for tailored treatments based on individual patient needs, potentially improving outcomes by minimizing unnecessary fluid administration and targeting specific conditions like gastrointestinal bleeding more effectively.

What evidence suggests that this trial's resuscitation methods could be effective for acute kidney injury in liver cirrhosis?

This trial will compare two resuscitation methods for acute kidney injury in liver cirrhosis. One group will receive a recommendation for resuscitation with crystalloids. Studies have shown that crystalloids can lower the risk of sudden kidney problems, reduce death rates, and lessen the need for treatments that replace kidney function. Research suggests that crystalloids might work better than colloids for these benefits. The other group will receive the standard of care with IV albumin, a common colloid, which might help control inflammation better than crystalloids. Some studies show no major difference in reducing severe kidney issues or death when using balanced crystalloids compared to normal saline. Overall, evidence suggests crystalloids play an important role in treating kidney problems, especially in terms of safety and reducing kidney complications. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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

Pregnant or nursing status

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

I have had a liver or kidney transplant in the past.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12433081/

Comparative Effectiveness of Fluid Resuscitation ... [17] found that crystalloids reduced the risk of AKI, mortality, and the need for renal replacement therapy (RRT) compared with colloids. However, excessive ...

2. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(23)00113-7/fulltext

Fluid resuscitation in patients with cirrhosis and sepsis Experimental data suggest that independent of volume expansion, albumin is superior to crystalloids at controlling systemic inflammation and ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2454911

Effect of a Buffered Crystalloid Solution vs Saline on Acute ... This randomized trial determines the effect of a buffered crystalloid compared with saline on renal complications among patients in the ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0735675719301494

Balanced crystalloids versus normal saline for fluid ... Use of a balanced crystalloid compared with normal saline did not reduce the mortality, risk of severe AKI or RRT use rate.

5. withpower.com withpower.com/trial/phase-fibrosis-6-2024-87444

Resuscitation Methods for Acute Kidney Injury in Liver ... Participants are monitored for safety and efficacy outcomes, including AKI response, vital status, and liver transplant status. Up to 90 days. Assessments at ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK537326/

Crystalloid Fluids - StatPearls - NCBI Bookshelf - NIH Crystalloid fluids are a type of intravenous solution employed in medical settings. Essential for fluid resuscitation in cases of hypovolemia, hemorrhage, ...

7. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(24)00214-9/fulltext

Acute kidney injury in patients with cirrhosis The following diagnostic criteria for HRS-AKI should be: a) cirrhosis with ascites; b) increase in serum creatinine ≥0.3 mg/dl (26.5 μmol/L) within 48 h or ≥50% ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1711584

Balanced Crystalloids versus Saline in Critically Ill Adults Data suggest that intravenous saline may be associated with hyperchloremic metabolic acidosis, acute kidney injury, and death. Crystalloid ...