High Dose Albumin for Ascites

Recruiting in Palo Alto (17 mi)

Overseen by Prasun Jalal, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Baylor College of Medicine

Must be taking: Albumin

Disqualifiers: TIPS, Cardiac, Malignant, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

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.

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}

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Baylor St' Lukes Medical center Houston, TX

Who Is Running the Clinical Trial?

Baylor College of Medicine Lead Sponsor

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] We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial.

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] To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications.

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] The number of available studies on the role of human serum albumin (HSA) in the treatment of cirrhotic ascites is currently limited. In this study, we aimed to investigated the parameters associated with diuretic therapy with HSA in patients with advanced cirrhotic ascites. The patient inclusion criteria were cirrhotic ascites and a serum albumin (Alb) concentration of

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] Albumin constitutes approximately one half of the proteins in the plasma and plays a pivotal role in modulating the distribution of fluid between body compartments. Hence it is commonly employed in cirrhotic patients in association with diuretics for the treatment of ascites. Nevertheless, its usefulness is controversial in this condition and well-stated only in some circumstances. The item of safety of the drug appears to be convincing due to the accurate cautions in the course of its preparation. Side effects are described in literature only as sporadic events. Indeed, albumin administration is effective to prevent the circulatory dysfunctions after large-volume paracentesis and renal failure and after Spontaneous Bacterial Peritonitis (SBP). Finally albumin represents, associated with vasoconstrictors, the therapeutic gold standard for the hepatorenal-syndrome (HRS). Physiopathological bases of the therapeutic use of albumin in hepatic cirrhosis consist in both hypoalbuminemia and portal hypertension consequences. In fact, cirrhotic patient with ascites, in spite of hydrosaline retention, shows an effective hypovolemia with peripheral arterial vasodilatation and increase in heart rate. Therefore the effectiveness of albumin administration in the treatment of ascites is due to its plasma volume expander property as well as its efficacy in restoring plasmatic oncotic pressure. Trials are in progress in order to define the effectiveness of the prolonged home-administration of human albumin in the treatment and prevention of ascites. Finally, it has been recently demonstrated that the binding, transport and detoxification capacities of human albumin are severely reduced in cirrhotics and this impairment correlates with the degree of liver failure. Therefore, the next challenge will be to determine whether the alterations of non-oncotic properties of albumin are able to forecast mortality in cirrhotics with ascites and exogenous albumin chronic administration will be effective in predicting and preventing such alterations.

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

Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites. [2020] In patients with cirrhosis, the clinical benefit of the treatment with human albumin for ascites is debated, and no data are available regarding refractory ascites. In this study, in patients with cirrhosis and refractory ascites, we assessed the effect of long-term albumin administration on emergent hospitalization and mortality.

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

Safety of human albumin--serious adverse events reported worldwide in 1998-2000. [2022] Previous pharmacovigilance studies have indicated a low rate of adverse events in patients receiving human albumin. However, the incidence of adverse events is likely to have been underestimated because of under-reporting. A more accurate estimate may be possible during a period such as 1998-2000, when awareness regarding albumin safety was heightened by publication of a meta-analysis.

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] Nanoparticle albumin-bound (nab)-paclitaxel was developed to improve paclitaxel solubility and does not need premedication to avoid infusion-related reactions associated with solvent-based (sb)-paclitaxel. We conducted a phase II trial to investigate the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer.

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] Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies.

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

Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. [2023] Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.

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] With the extensive application of paclitaxel for injection (albumin-bound), its adverse reactions have also received increasing attention.

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

[The use of albumin infusion in decompensated liver cirrhosis]. [2007] For patients with refractory ascites, paracentesis is the standard therapy and for many it is the only treatment option. When more than five litres of ascitic fluid are removed, the use of a plasma expander effectively prevents "postparacentesis circulatory dysfunction", which is associated with a high mortality. Randomised controlled studies show that albumin is more effective than synthetic plasma expanders in the prevention of this complication. In selected patients with ascites, long-term administration of albumin may improve the diuretic response. A randomised controlled study in patients with spontaneous bacterial peritonitis has demonstrated that treatment with albumin infusion in addition to an antibiotic reduces the incidence of hepatorenal syndrome. Albumin infusion in combination with the administration of a vasopressin analogue may be able to reverse established hepatorenal syndrome; however, no controlled studies have been published. Whereas the use of albumin infusion with large-volume paracentesis is strongly supported by the available evidence, additional conclusive studies of the use of albumin for spontaneous bacterial peritonitis are awaited.

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] In patients with cirrhosis, ascites accumulates because of sodium retention, triggered by a reduction of the effective arterial blood volume, and imbalanced Starling forces in the splanchnic area due to portal hypertension and hypoalbuminemia. Albumin is the ideal plasma expander in this setting, since it ameliorates systemic and reneal haemodynamics, so reducing sodium retention, and increases oncotic pressure in the splanchnic compartment. In particular, albumin proved useful in patients treated with diuretics, as demonstrated by a randomised study performed at our Instituition in which 126 ascitic inpatients were treated according to a stepped-care diuretic regimen. In fact, patients receiving diuretics plus albumin (n = 63) had a higher cummulative rate of response (p