Albumin Human for Burns

(ABRUPT2 Trial)

Recruiting at 25 trial locations

Overseen By Mary Beth Lawless, RN, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: American Burn Association

Must not be taking: FFP, HTS, HES, Vitamin C

Disqualifiers: Significant trauma, Electrical burns, Pregnancy, Renal insufficiency, Hepatic disease, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

400 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares two ways of giving fluids to adults with severe burns. One way uses a mix of saltwater and protein solutions, while the other uses just saltwater. The goal is to see which way better maintains blood pressure and organ function by replacing lost fluids.

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, certain treatments like fresh frozen plasma, hypertonic saline, hydroxyethyl starch, high dose Vitamin C, and human albumin are not allowed within 48 hours of injury.

What data supports the effectiveness of the drug Albumin Human for treating burns?

Research suggests that albumin supplementation in burn patients does not significantly improve outcomes such as organ function or recovery, and its benefits for correcting low albumin levels in these patients are unclear. ^{1 2 3 4 5}

Is Albumin Human safe for use in humans?

Human albumin is generally considered a safe blood product with rare adverse events. Studies show that it does not provoke an immune response and has a low rate of mild side effects, making it safe for use in various medical treatments. ^{3 6 7 8 9}

How does the drug Albumin Human differ from other treatments for burns?

Albumin Human is unique because it is a natural protein solution used to maintain blood volume and pressure, which can help reduce swelling and stabilize blood pressure in burn patients. Unlike other treatments, it specifically targets hypoalbuminemia (low albumin levels) that often occurs after major burns, although its benefits in this context are still debated. ^{1 3 4 10 11}

Research Team

David G Greenhalgh, MD

Principal Investigator

UC Davis Health

Eligibility Criteria

Adults with severe burns covering at least 25% of their body, admitted to a burn center within 12 hours of injury and needing fluid resuscitation can join. Excluded are those with major trauma, certain pre-injury conditions like kidney or liver disease, heart dysfunction, pregnancy, or specific treatments received before the trial.

Inclusion Criteria

I am 18 years old or older.

I am scheduled for a procedure to receive fluids for my condition.

I was admitted to a burn center within 12 hours after getting burned.

Exclusion Criteria

You have recently experienced a serious injury or accident.

I had surgery to remove a burn wound within 2 days of the injury.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive fluid resuscitation with either Lactated Ringer's alone or Lactated Ringer's with 5% albumin for the first 48 hours post burn

48 hours

Continuous monitoring

Acute Monitoring

Participants are monitored for acute kidney injury, organ function, and other complications up to 96 hours post burn

96 hours

Follow-up

Participants are monitored for survival and hospital discharge outcomes

28 days

Treatment Details

Interventions

• Albumin Human

Trial Overview The study is testing two ways to help adults recover from severe burns by giving fluids. One group gets lactated Ringer's solution plus albumin (a protein), while the other gets just lactated Ringer's. The goal is to see which method works better for resuscitation.

Participant Groups

Group I: Crystalloid Active Control 1 Intervention

Subjects in the crystalloid group will receive fluid resuscitation with Lactated Ringer's titrated each hour to achieve a urine output of 0.5-1mL/kg predicted body weight.

Group II: Colloid Active Control 1 Intervention

Subjects in the colloid group will receive fluid resuscitation with Lactated Ringer's and 5% human albumin solution introduced no earlier than 8 hours post burn and no later than 12 hours post burn in a ratio by volume of 1/3 albumin to 2/3 Lactated Ringer's, and titrated each hour to achieve a urine output of 0.5-1mL/kg (milliliter/kilogram) predicted body weight.

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

Approved in United States as Albumin Human for:

• Hypovolemia
• Hypoalbuminemia
• Burns
• Pancreatitis
• Peritonitis
• Postoperative Albumin Loss
• Shock
• Adult Respiratory Distress Syndrome
• Hemolytic Disease of the Newborn

Approved in European Union as Albumin Human for:

• Hypovolemia
• Hypoalbuminemia
• Burns
• Pancreatitis
• Peritonitis
• Postoperative Albumin Loss
• Shock

Who Is Running the Clinical Trial?

American Burn Association

Lead Sponsor

Trials

11

Recruited

2,200+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study comparing 43 burn patients, routine supplementation of 5% human albumin did not improve clinical outcomes such as organ function, length of hospital stay, or mortality rates, despite increasing serum albumin levels significantly.

The cost of albumin supplementation was over four times higher than the control group, highlighting that it is an expensive intervention without demonstrated benefits for patients with major burns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin supplementation for hypoalbuminemia following burns: unnecessary and costly! Melinyshyn, A., Callum, J., Jeschke, MC., et al.[2018]

Certain human albumin solutions can increase the expression of adhesion molecules like ICAM-1 and E-selectin on endothelial cells, which may contribute to worsened outcomes in critically ill patients.

The study found that two specific albumin preparations (HA1 and HA4) from the same manufacturer had significant effects on adhesion molecule expression, while others did not, suggesting variability in the inflammatory potential of different albumin products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules. Nohé, B., Dieterich, HJ., Eichner, M., et al.[2019]

In a phase I study involving 82 patients with acute ischemic stroke, high-dose human albumin (ALB) therapy showed a significant increase in the likelihood of achieving a good outcome compared to lower doses, with an 81% greater probability of favorable results at the highest doses.

The combination of high-dose ALB with standard tPA treatment resulted in a threefold increase in the chances of a good outcome, indicating a potential synergistic effect that supports further investigation in a larger trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis. Palesch, YY., Hill, MD., Ryckborst, KJ., et al.[2016]

In a study of 38 major burn patients with burns covering 20% or more of their body, administering high doses of human albumin solutions did not significantly improve mortality rates or other clinical outcomes.

The research indicated that while persistent hypoalbuminemia is common in major burn patients, large amounts of albumin supplements do not provide significant benefits in terms of renal function, mechanical ventilation duration, or length of hospital stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin supplementation may have limited effects on prolonged hypoalbuminemia in major burn patients: An outcome and prognostic factor analysis. Chen, YF., Ma, H., Perng, CK., et al.[2021]

In a multicenter trial involving 42 adult burn patients, treatment with 5 percent human albumin did not significantly reduce the severity of multiple organ dysfunction (MODS) compared to standard fluid resuscitation with Ringer's lactate over 14 days.

The study found no significant differences in patient demographics or baseline health status between the albumin and control groups, indicating that albumin resuscitation does not provide additional benefits for organ function in burn patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score. Cooper, AB., Cohn, SM., Zhang, HS., et al.[2018]

In a study involving 34 healthy volunteers, Albunex, an ultrasound contrast agent made from heat-aggregated human albumin, did not induce any immunological response, as no IgE or IgG antibodies were detected after multiple injections.

Additionally, tests showed that Albunex did not cross-react with cat albumin-specific IgE, indicating it is unlikely to provoke allergic reactions in individuals with cat allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres. Christiansen, C., Vebner, AJ., Muan, B., et al.[2018]

The study measured prekallikrein activator (PKA) levels in various commercial human albumin batches, finding moderate amounts of PKA present without any reported side reactions, suggesting that PKA is not a significant safety concern.

Despite some discussions about certain batches of human albumin causing adverse reactions, the findings indicate that trace amounts of PKA do not correlate with these side effects, reinforcing the overall safety of human albumin as a blood product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prekallikrein activator levels and side effects with human albumin preparations. Lüben, G., Quast, U., Geiger, H.[2006]

Thirteen commercial preparations of human albumin showed significant variability in fatty acid content, ranging from 0.03 to 9 mol of fatty acid per mol of albumin, which affects their drug-binding properties.

The binding affinity of fluorescent probes and the displacement by drugs like ibuprofen and phenylbutazone varied greatly among the albumin preparations, indicating that both the source and fatty acid content of albumin should be considered in pharmacological studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fatty acid content and drug binding characteristics of commercial albumin preparations. Birkett, DJ., Myers, SP., Sudlow, G.[2019]

In a study involving 40 patients undergoing therapeutic plasmapheresis, Albumex 5 showed a reaction rate of 12.1%, compared to 8.3% for 5% normal serum albumin (5% NSA), but this difference was not statistically significant (p = 0.37).

Both Albumex 5 and 5% NSA had low rates of adverse events, with none classified as serious, indicating that Albumex 5 can be considered a safe option for plasma replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety study of Albumex 5, a human albumin solution produced by ion exchange chromatography. Wolf, M., Kronenberg, H., Dodds, A., et al.[2019]

In a study of 39,684 burn patients, the use of albumin for volume replacement was linked to significantly higher hospital mortality rates, with odds ratios indicating a 20.58 times higher risk for men with moderate burns and 40.97 times higher for women.

The increased risk of death associated with albumin use was consistent across different patient characteristics, suggesting that albumin may not be a safe option for managing burn patients compared to other volume replacement solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of albumin as a risk factor for hospital mortality among burn patients in Brazil: non-concurrent cohort study. Caleman, G., Morais, JF., Puga, ME., et al.[2019]

Human albumin is a safe and effective solution for volume loading, with a low risk of infectious complications when produced under controlled conditions, although some rare anaphylactoid reactions can occur.

There is a documented risk of contamination with metals like aluminum, highlighting the need for strict manufacturing procedures and ongoing monitoring to ensure long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immediate and late complications of human albumin use]. Quaranta, JF.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Albumin supplementation for hypoalbuminemia following burns: unnecessary and costly! [2018]

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

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules. [2019]

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

The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis. [2016]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Albumin supplementation may have limited effects on prolonged hypoalbuminemia in major burn patients: An outcome and prognostic factor analysis. [2021]

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

Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Prekallikrein activator levels and side effects with human albumin preparations. [2006]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The fatty acid content and drug binding characteristics of commercial albumin preparations. [2019]

9. England pubmed.ncbi.nlm.nih.gov

A safety study of Albumex 5, a human albumin solution produced by ion exchange chromatography. [2019]

10. Brazil pubmed.ncbi.nlm.nih.gov

Use of albumin as a risk factor for hospital mortality among burn patients in Brazil: non-concurrent cohort study. [2019]

11. France pubmed.ncbi.nlm.nih.gov

[Immediate and late complications of human albumin use]. [2019]