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

Trial Summary

What is the purpose of this trial?

Hypothesis: Improvement in cognitive dysfunction with IV albumin in patients with cirrhosis with prior HE and MHE lasts for several weeks after albumin infusion has ended, and is due to persistent improvement in inflammatory markers, endothelial dysfunction, albumin function and gut microbial changes. This will be a single-arm, single-blind sequential trial of IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health related quality of life (HRQOL) testing with each subject acting as their own control.

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.

What evidence supports the effectiveness of the drug albumin for treating hepatic encephalopathy?

Research suggests that human albumin may help reduce the incidence of hepatic encephalopathy (a brain disorder caused by liver disease) and improve outcomes in patients with cirrhosis by addressing inflammation and oxidative stress. However, its effectiveness can vary, as some studies show no significant impact in certain situations, like after specific liver procedures. ^{1 2 3 4 5}

Is albumin safe for use in humans?

Research suggests that albumin is generally safe for use in humans, though some studies have noted potential adverse events like coagulation disorders (problems with blood clotting) in certain cases. More studies are needed to fully understand its safety profile, especially in specific conditions like liver failure. ^{2 3 4 6 7}

How does the drug albumin differ from other treatments for hepatic encephalopathy?

Albumin is unique in treating hepatic encephalopathy because it has anti-inflammatory properties that may help reduce systemic inflammation and oxidative stress, which are believed to contribute to the condition. Unlike other treatments, albumin infusion can improve outcomes in cirrhotic patients by potentially lowering the incidence of hepatic encephalopathy. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

No effect of albumin infusion on the prevention of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. [2018]

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

Low Prealbumin Levels Were Associated with Increased Frequency of Hepatic Encephalopathy in Hepatitis B Virus (HBV)-Related Decompensated Cirrhosis. [2023]

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

Albumin therapy for hepatic encephalopathy: current evidence and controversies. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Association of serum albumin level with incidence and mortality of overt hepatic encephalopathy in cirrhosis during hospitalization. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Diagnostic value of albumin-bilirubin grade combined with serum ammonia in cirrhosis with hepatic encephalopathy]. [2018]

6. Spain pubmed.ncbi.nlm.nih.gov

[Artificial liver support. Literature review]. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of albumin infusion for overt hepatic encephalopathy: A systematic review and meta-analysis. [2022]