Albumin for Hepatic Encephalopathy

(HEAL-LAST Trial)

Overseen By Jasmohan Bajaj, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center

Must be taking: Lactulose, Rifaximin

Disqualifiers: Infection, Alcohol abuse, Heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if IV albumin treatment can improve cognitive issues in people with cirrhosis (severe liver scarring) who have previously experienced hepatic encephalopathy (a brain disorder due to liver issues). Participants will receive either albumin or a placebo for comparison. The trial explores whether this treatment can lead to lasting improvements in inflammation and gut health. Suitable candidates have cirrhosis and have experienced cognitive issues managed by specific medications for at least a month. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have prior HE controlled by lactulose or rifaximin for at least one month, suggesting you may need to continue these medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that albumin is usually safe for people with liver problems. Studies have found that long-term use of albumin can reduce the risk of death and other complications in these patients. In one study, albumin improved thinking and quality of life for those experiencing liver-related brain fog. Another study demonstrated that albumin was both effective and safe for patients with sudden liver failure. Overall, this evidence suggests that albumin is a safe choice for people with liver conditions, including those in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Albumin is unique because it uses a new approach to tackle hepatic encephalopathy. While traditional treatments often focus on managing symptoms with medications like lactulose or rifaximin, albumin works differently by potentially addressing the underlying issues related to blood flow and toxin removal in the liver. Researchers are excited about albumin because it could improve liver function and reduce inflammation, offering a more comprehensive solution to managing hepatic encephalopathy. Additionally, its delivery through IV infusion ensures precise dosing, which might lead to quicker and more effective results compared to current oral medications.

What evidence suggests that albumin might be an effective treatment for hepatic encephalopathy?

This trial will compare the effects of albumin with a placebo in treating hepatic encephalopathy. Research has shown that albumin can improve brain function in people with liver problems, such as cirrhosis. Studies have found that using albumin in plasma exchange effectively treats hepatic encephalopathy, a brain condition caused by liver issues. Increasing evidence suggests that long-term albumin therapy might enhance thinking skills and prevent the condition from recurring in patients with severe hepatic encephalopathy. Although some studies did not achieve their main goals, albumin still showed potential in improving survival rates for those with liver problems. Overall, albumin appears to be a promising treatment for enhancing brain function in people with liver-related conditions. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with liver cirrhosis and low platelets, diagnosed through various methods like biopsy or imaging. They must have cognitive impairment from hepatic encephalopathy (HE) but be stable on treatment for at least a month. People with severe HE, unclear diagnosis of cirrhosis, heart failure, recent alcohol abuse, allergies to albumin or infections are excluded.

Inclusion Criteria

I have been diagnosed with cirrhosis through tests or signs like low platelets or specific liver enzyme ratios.

I have had brain function issues due to liver disease but controlled it with medication for over a month.

You have trouble with your memory and thinking abilities, as shown by specific tests.

Exclusion Criteria

Unlikely to be adherent to the study

I have not had an infection in the last month.

I need or will need albumin infusions regularly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health-related quality of life testing

8 weeks

Weekly visits for infusion and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on cognitive improvement and inflammatory markers

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Albumin

Trial Overview The study tests if intravenous albumin can improve brain function in patients with liver cirrhosis who've had HE. Participants receive IV albumin and saline over 8 weeks and serve as their own control while undergoing cognitive tests and health quality assessments.

How Is the Trial Designed?

Group I: Albumin Active Control 1 Intervention

IV Albumin at 1.5g/kg ideal body weight

Group II: Placebo Placebo Group 1 Intervention

Saline given at the same volume as the albumin on visits the patients are assigned to it

Albumin is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Albumin for:

• Acute Liver Failure
• Adult Respiratory Distress Syndrome
• Burns
• Cardiopulmonary Bypass
• Hypoalbuminemia
• Hemodialysis
• Hypovolemia
• Ovarian Hyperstimulation Syndrome

Approved in European Union as Albumin for:

• Hypoalbuminemia
• Hypovolemia
• Ascites
• Spontaneous Bacterial Peritonitis
• Hepatic Encephalopathy
• Hepatorenal Syndrome

Approved in Japan as Albumin for:

• Hypoalbuminemia
• Hypovolemia
• Ascites
• Spontaneous Bacterial Peritonitis

Who Is Running the Clinical Trial?

Hunter Holmes Mcguire Veteran Affairs Medical Center

Lead Sponsor

Trials

37

Recruited

21,600+

Grifols Biologicals, LLC

Industry Sponsor

Trials

33

Recruited

9,500+

Published Research Related to This Trial

Extracorporeal albumin dialysis systems, including MARS, Prometheus, and Biologic-DT, effectively reduce toxic substances like bilirubin and creatinine in patients with liver failure, as shown in 10 controlled trials.

While some studies indicated improvements in hepatic encephalopathy and survival, safety assessments revealed coagulation disorders as a common adverse event, highlighting the need for more standardized research on long-term outcomes and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Artificial liver support. Literature review]. Lafuente, S., Bertran, MJ., Escorsell, A.[2018]

Hepatic encephalopathy (HE) affects 16-21% of patients with end-stage cirrhosis, and recent studies suggest that systemic inflammation and oxidative stress contribute to its development.

Human albumin, known for its anti-inflammatory properties, is being explored as a potential treatment and preventive measure for HE in patients with advanced cirrhosis, highlighting its therapeutic promise in managing this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin therapy for hepatic encephalopathy: current evidence and controversies. Wong, YJ., Loo, JH.[2023]

In a study of 2376 cirrhotic patients, lower serum albumin (ALB) levels were found to be an independent risk factor for developing overt hepatic encephalopathy (HE), with a significant predictive value (AUC = 0.770) and a critical cut-off at ≤31.6 g/l.

Among 183 patients with overt HE, lower ALB levels also correlated with increased mortality risk, indicating that ALB levels (AUC = 0.737) can be used to predict death from HE, with a cut-off value of ≤22.8 g/l.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of serum albumin level with incidence and mortality of overt hepatic encephalopathy in cirrhosis during hospitalization. Bai, Z., Guo, X., Tacke, F., et al.[2022]

In a study of 139 patients, combining albumin-bilirubin (ALBI) grade with serum ammonia levels significantly improved the diagnosis of hepatic encephalopathy (HE) in cirrhosis patients, showing a high sensitivity of 93.9% and specificity of 93.2%.

The study found that both ALBI and blood ammonia levels increased with the severity of liver disease, indicating their potential as reliable biomarkers for assessing the progression of cirrhosis and the presence of HE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnostic value of albumin-bilirubin grade combined with serum ammonia in cirrhosis with hepatic encephalopathy]. Hou, YL., Gao, MD., Guo, HY., et al.[2018]

Albumin infusion significantly reduces the risk of overt hepatic encephalopathy (OHE) in cirrhosis patients, with a pooled odds ratio of 0.43 based on 12 studies involving 2,087 subjects.

In addition to lowering the risk of OHE, albumin infusion is also associated with a reduced risk of inpatient mortality (odds ratio of 0.36), suggesting it may improve overall outcomes for patients with decompensated cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of albumin infusion for overt hepatic encephalopathy: A systematic review and meta-analysis. Teh, KB., Loo, JH., Tam, YC., et al.[2022]

In a study of 23 patients undergoing TIPS, albumin infusion did not significantly reduce the incidence of overt hepatic encephalopathy (HE) compared to historical controls, with rates of 34% in the albumin group and 31% in controls during the first month.

Both groups showed similar changes in venous blood ammonia levels and psychometric test results, indicating that albumin infusion does not play a beneficial role in preventing post-TIPS HE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No effect of albumin infusion on the prevention of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Riggio, O., Nardelli, S., Pasquale, C., et al.[2018]

In a study of 262 patients with HBV-related decompensated liver cirrhosis, low prealbumin levels were found to be significantly associated with a higher incidence of hepatic encephalopathy (HE).

Prealbumin demonstrated superior diagnostic performance for predicting HE compared to traditional scoring models like MELD and Child-Turcotte-Pugh, with an area under the ROC curve of 0.781.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Prealbumin Levels Were Associated with Increased Frequency of Hepatic Encephalopathy in Hepatitis B Virus (HBV)-Related Decompensated Cirrhosis. Li, J., Du, M., Li, H., et al.[2023]

Citations

1. grifols.com grifols.com/en/view-news/-/news/grifols-announces-topline-phase-3-data-on-long-term-albutein-albumin-human-usp-therapy-for-decompensated-cirrhosis-with-ascites

Grifols announces topline phase 3 data on long-term ... Though primary endpoint of one-year transplant-free survival was not met, trial showed improved transplant-free survival, mortality and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10966298/

Effect of plasma exchange with albumin replacement on ... PE using albumin 5% (PE-A5%) as a replacement fluid is an effective and safe treatment in patients with acute liver failure, improving hepatic encephalopathy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03585257

HEAL STUDY (Hepatic Encephalopathy and Albumin Study) This 6 week trial will study changes in cognition, HRQOL and inflammation in patients with covert HE after prior overt HE using multiple IV albumin infusions vs ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1665268124005349

The burden of hepatic encephalopathy and the use ... There is increasing evidence that prolonged or long-term albumin therapy can help improve cognition in OHE and prevent recurrence.

5. journals.lww.com journals.lww.com/hep/fulltext/2025/01000/controversies_regarding_albumin_therapy_in.26.aspx

Controversies regarding albumin therapy in cirrhosis Serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7268936/

Albumin: Indications in chronic liver disease - PMC Recently, evidence has shown that long-term albumin administration in patients with decompensated cirrhosis reduces 18-month mortality and the incidence of ...