High Dose Albumin for Ascites

Overseen By Prasun Jalal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must be taking: Albumin

Disqualifiers: TIPS, Cardiac, Malignant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 2

Duration: 12 months

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial focuses on patients with refractory ascites who are already on maximum tolerable doses of diuretics, it seems likely that you may continue your current treatment.

What data supports the effectiveness of the drug for treating ascites?

Research shows that long-term use of human albumin can improve survival and reduce hospitalizations in patients with cirrhosis and ascites. It is also effective in preventing complications like kidney failure and circulatory issues after certain medical procedures. ^{1 2 3 4 5}

Is high dose albumin generally safe for humans?

Previous studies have shown that human albumin has a low rate of serious side effects, although some incidents might be under-reported. Overall, it is considered safe for use in humans. ^{6 7 8 9 10}

How does the drug albumin differ from other treatments for ascites?

Albumin is unique because it acts as a plasma expander, helping to restore blood volume and pressure, which can improve the body's response to diuretics and prevent complications after fluid removal. It is particularly effective in preventing circulatory dysfunction after large-volume paracentesis and in reducing the risk of kidney problems in patients with liver cirrhosis. ^{1 3 4 11 12}

What is the purpose of this trial?

Advanced cirrhosis with complications is a serious problem imposing a heavy financial burden on health care system. Moreover, ascites is associated with increase in mortality rates among cirrhotic patients. Ascites pathogenesis is multifactorial including: portal hypertension; splanchnic and peripheral arterial vasodilation; and neurohumoral activation. Current management strategies include dietary sodium restriction and diuretic therapy, however, this strategy put patients at the risk of intravascular volume depletion, renal impairment, hepatic encephalopathy and hyponatremia. Moreover, around 10% of patients do not respond to this strategy (termed: diuretics resistant) with 50% of them die within 6 months. This sub-group is managed by frequent large volume paracentesis along with intravenous albumin administration and are usually considered for liver transplantation (LT) and TIPS. Nonetheless, Frequent paracentesis increases the risk of infection, bleeding, bowel perforation, paracentesis-induced circulatory dysfunction (PICD) and renal dysfunction in this sub-group of patients. The beneficial effect of human albumin might result from blood volume expansion tapering activated vasoconstrictor and sodium-retaining systems improving renal perfusion, hence regular infusion of albumin may be beneficial to prevent development of ascites and to improve survival. The positive effects of albumin are supported by previous studies; Romanelli et al, showed a significant increase in survival rate among cirrhotic patients with ascites when compared to those who did not receive albumin. Moreover, a randomized multicenter open label trial published in lancet last year, demonstrated that long term albumin administration improved 18-month survival, decreased the use of paracentesis and decrease in the incidence of cirrhosis related complications among cirrhotic patients with ascites. As of today, there's a limited use of regular high dose albumin in cirrhotic patients with ascites in US, despite being used elsewhere in the world as previously stated. The investigators wish to study long-term efficacy of human albumin administration in patients with decompensated cirrhosis to assess safety and efficacy, and prevention of complications of cirrhosis.

Research Team

Prasun Jalal, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with liver cirrhosis and refractory ascites, which means their body retains fluid despite maximum diuretic treatment and often needs excess fluid removed.

Inclusion Criteria

My ascites hasn't improved despite maximum diuretic treatment and needs frequent draining.

I am older than 18 years.

I have been diagnosed with liver cirrhosis.

Exclusion Criteria

I have never had liver cirrhosis.

I have fluid in my abdomen not caused by heart or cancer issues.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either high-dose albumin or standard care for up to one year

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Albumin

Trial Overview The study tests the long-term effects of high-dose human albumin in patients with advanced liver disease to see if it can prevent complications and improve survival by expanding blood volume.

Participant Groups

Group I: Intervention arm Experimental Treatment 1 Intervention

the intervention group will receive intravenous human albumin at a dose of (1g/kg), with a minimum dose of 50g and a maximum dose of 100g, plus SOC

Group II: Control arm Active Control 1 Intervention

the control arm will receive the standard of care (SOC), including moderate sodium restriction, maximal daily tolerated doses of diuretics, and post-paracentesis albumin

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

Long-term administration of albumin significantly improved the normalization rate of hyponatremia in patients with ascites, achieving 45% normalization compared to 28% with standard treatment after one month.

Patients receiving long-term albumin treatment experienced a much lower incidence of at least moderate hyponatremia over 18 months, with an incidence rate ratio of 0.245, indicating a strong protective effect against worsening hyponatremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database. Zaccherini, G., Baldassarre, M., Tufoni, M., et al.[2023]

In a study of 100 patients with first-onset ascites, those receiving long-term albumin treatment alongside diuretics had a significantly higher survival rate compared to those receiving diuretics alone, with an average increase in survival of 16 months.

Patients treated with albumin also experienced a much lower recurrence rate of ascites (51% compared to 94% in the control group), indicating that albumin administration can effectively reduce complications associated with ascites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. Romanelli, RG., La Villa, G., Barletta, G., et al.[2019]

In a study of 38 patients with advanced cirrhotic ascites, the administration of human serum albumin (HSA) significantly increased serum albumin levels and led to weight loss, indicating its efficacy in managing this condition.

The weight loss observed was directly correlated with the total amount of HSA administered, suggesting that higher doses may enhance the therapeutic effects in patients undergoing diuretic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of diuretic therapy with human serum albumin to the management of ascites in patients with advanced liver cirrhosis: A prospective cohort study. Nakamura, T., Sata, M., Hiroishi, K., et al.[2021]

Albumin is effective in treating ascites in cirrhotic patients, particularly in preventing circulatory dysfunction after procedures like large-volume paracentesis and in managing hepatorenal syndrome, due to its properties as a plasma volume expander and its ability to restore oncotic pressure.

The safety profile of albumin is generally favorable, with side effects being rare, and ongoing trials are exploring the long-term benefits of home administration of albumin for preventing and treating ascites in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives. Facciorusso, A., Nacchiero, MC., Rosania, R., et al.[2022]

In a study of 70 patients with cirrhosis and refractory ascites, long-term administration of human albumin significantly reduced 24-month mortality (41.6% vs 65.5%) compared to standard medical care.

Patients receiving albumin treatment experienced a longer period free from emergent hospitalizations and a lower incidence of complications such as hepatic encephalopathy and infections, indicating improved overall health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites. Di Pascoli, M., Fasolato, S., Piano, S., et al.[2020]

During the period from 1998 to 2000, a total of 1.62 x 10^7 doses of human albumin were distributed, with reported serious adverse events being rare, at an incidence of 5.28 per 10^6 doses.

The study found that while the incidence of serious adverse events was higher during this period compared to earlier years, this increase is likely due to improved reporting practices, reinforcing the overall excellent safety record of human albumin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of human albumin--serious adverse events reported worldwide in 1998-2000. Vincent, JL., Wilkes, MM., Navickis, RJ.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

Nab-PTX (nanoparticle albumin-bound paclitaxel) shows promising efficacy as a neoadjuvant chemotherapy for operable breast cancer, with a pathological complete response (pCR) rate of 40.5% for HER2-rich cancers and 26.3% for triple-negative breast cancers, based on a meta-analysis of 16 studies involving 753 patients.

The treatment is generally safe, with manageable side effects such as neutropenia and peripheral sensory neuropathy, and most patients recover from these adverse effects, making nab-PTX a viable option for aggressive breast cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study). Futamura, M., Oba, M., Masuda, N., et al.[2022]

Albumin is increasingly used as a drug carrier in clinical settings, with technologies including drug coupling, protein conjugation, and drug encapsulation in albumin nanoparticles, which enhance drug delivery to tumors due to albumin's accumulation in solid tumors.

Abraxane, an albumin nanoparticle formulation of paclitaxel, has been approved for metastatic breast cancer, while other albumin-based therapies like Levemir for diabetes and Albuferon for hepatitis C are in advanced clinical stages, showcasing the versatility and efficacy of albumin as a drug delivery system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. Kratz, F.[2023]

A study analyzing 1659 adverse events related to albumin-bound paclitaxel revealed that most adverse reactions occurred in females aged 45-64, affecting various organ systems, particularly blood and lymphatic systems.

The research identified 20 unexpected adverse drug reactions, including macular edema and lymphopenia, which are not listed on drug labels, highlighting the need for careful monitoring of patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety signals of albumin-bound paclitaxel: Data mining of the Food and Drug Administration adverse event reporting system. Wang, Y., Liu, X.[2023]

In patients with refractory ascites, using albumin as a plasma expander during large-volume paracentesis (removing more than five liters of fluid) is more effective than synthetic alternatives in preventing serious complications like postparacentesis circulatory dysfunction, which can be life-threatening.

Long-term albumin administration may enhance diuretic response in certain patients, and it has been shown to reduce the incidence of hepatorenal syndrome when combined with antibiotics in cases of spontaneous bacterial peritonitis, although further studies are needed to confirm its effectiveness in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of albumin infusion in decompensated liver cirrhosis]. Schmidt, LE., Ring-Larsen, H.[2007]

In a study of 126 patients with cirrhosis and ascites, those treated with diuretics plus albumin had a significantly higher response rate and shorter hospital stays compared to those receiving diuretics alone.

Outpatient treatment with albumin (25 g/week) not only reduced the likelihood of developing ascites and readmissions but also improved patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the use of albumin of value in the treatment of ascites in cirrhosis? The case in favour. Laffi, G., Gentilini, P., Romanelli, RG., et al.[2019]

References

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

Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database. [2023]

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

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. [2019]

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

Contribution of diuretic therapy with human serum albumin to the management of ascites in patients with advanced liver cirrhosis: A prospective cohort study. [2021]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives. [2022]

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

Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety of human albumin--serious adverse events reported worldwide in 1998-2000. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study). [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. [2023]

10. India pubmed.ncbi.nlm.nih.gov

Safety signals of albumin-bound paclitaxel: Data mining of the Food and Drug Administration adverse event reporting system. [2023]

11. Denmark pubmed.ncbi.nlm.nih.gov

[The use of albumin infusion in decompensated liver cirrhosis]. [2007]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Is the use of albumin of value in the treatment of ascites in cirrhosis? The case in favour. [2019]