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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to manage fluid resuscitation (replacing lost body fluids) in adults with severe burns covering at least 25% of their body. It compares two strategies: one using only Lactated Ringer's solution and another using a combination of Lactated Ringer's and human albumin (a protein solution used to restore blood volume). Individuals who have suffered a significant burn and are admitted to a burn center within 12 hours of injury might be suitable for this study. The goal is to determine which method better supports recovery and overall health in burn patients. As an unphased trial, this study allows participants to contribute to important research that could enhance future burn care practices.

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 prior data suggests that this fluid resuscitation strategy is safe for burn patients?

Research has shown that human albumin often treats low blood volume and low albumin levels in the blood. It is also used for severe burns, typically not until at least 12 hours after the burn. This suggests it has been considered for similar uses before.

Regarding safety, human albumin is generally well-tolerated, but caution is necessary. It should be used carefully when increasing blood volume could be risky. For instance, in individuals with certain heart or kidney problems, extra fluid might cause complications.

Side effects are usually mild. Some individuals might experience a slight increase in blood pressure or a reaction at the injection site. These side effects are uncommon but possible. Overall, human albumin has been used in various treatments, demonstrating a level of safety and tolerance in patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using albumin human for burn treatment because it introduces a new way to manage fluid resuscitation. Unlike the standard crystalloid-based approaches, which rely solely on solutions like Lactated Ringer's, the colloid method incorporates 5% human albumin. This combination helps better maintain fluid balance and potentially improves outcomes by enhancing circulation and tissue perfusion. By adding albumin, researchers hope to reduce the volume of fluids needed and improve recovery time for burn patients.

What evidence suggests that Albumin Human might be an effective treatment for burns?

Research has shown that albumin can aid recovery in people with burn injuries. Albumin is often used to treat low blood volume, which occurs when there isn't enough liquid in the blood vessels, and low levels of albumin, a protein in the blood. In this trial, participants in the colloid group will receive fluid resuscitation with Lactated Ringer's and 5% human albumin solution, administered between 8 and 12 hours post-burn. This approach aims to stabilize blood volume and support recovery. Meanwhile, the crystalloid group will receive fluid resuscitation with Lactated Ringer's alone. Although studies suggest benefits from using albumin, the evidence remains somewhat limited, necessitating further research to fully understand its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

David G Greenhalgh, MD

Principal Investigator

UC Davis Health

Are You a Good Fit for This Trial?

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 scheduled for a procedure to receive fluids for my condition.

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

Over 25% of my body is 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4851230/

Albumin in Burn Shock Resuscitation: A Meta-Analysis of ... This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited.

2. mayoclinic.org mayoclinic.org/drugs-supplements/albumin-human-intravenous-route/description/drg-20454125

Albumin human (intravenous route) - Side effects & uses Albumin (human) injection is used to treat low blood volume (hypovolemia). It is also used to treat low albumin levels in the blood (hypoalbuminemia)

3. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a43c5ed6-7423-4ee5-8acb-5fccc2d7b6cc

Label: HUMAN ALBUMIN GRIFOLS (albumin- human solution In burns, therapy usually starts with administration of large volumes of crystalloid solution to maintain plasma volume. After 24 hours: initial dose of 25 g ...

4. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---ALBUMINEX-%2825---Clean%29.pdf

Package Insert - ALBUMINEX 25 ALBUMINEX 25% is indicated in patients with severe burn injury (> 20% total body surface area), but not until at least 12 to 24 hours after the burn, in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S001236922400285X

Use of Intravenous Albumin: A Guideline From the ... Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of ...

6. drugs.com drugs.com/mtm/human-albumin-grifols-human.html

Human Albumin Grifols human Uses, Side Effects & ... Albumin is used to replace blood volume loss resulting from trauma such as a severe burns or an injury that causes blood loss. This medicine is also used to ...

7. grifols.com grifols.com/en/view-news/-/news/grifols-introduces-albutein-flexbag-albumin-human-usp-in-5-and-25-concentrations-a-more-convenient-option-for-healthcare-professionals

Grifols introduces ALBUTEIN FlexBag™ (Albumin [Human] ... Use albumin with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient.