Albumin for Acute Kidney Injury

(ALTER-AKI Trial)

Recruiting at 16 trial locations

Overseen By Irene Watpool, RN BScN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Disqualifiers: End-stage kidney disease, Kidney transplant, Advanced cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

856 Participants Needed

Trial Summary

What is the purpose of this trial?

Study objectives: To determine whether, in critically ill patients with Acute Kidney Injury requiring renal replacement therapy (AKI-RRT), randomization to receive intravenous hyperoncotic albumin 20-25% (100 mL X two doses) compared to control/placebo normal saline boluses (100 mL X two doses) given during RRT sessions, leads to: 1. An increase in organ support-free days (primary outcome) at 28 days following randomization; and 2. An increase in RRT-free days (principal secondary outcome) at 28 days following randomization.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Albumin for Acute Kidney Injury?

Some studies suggest that hyperoncotic albumin (a concentrated form of albumin) may help improve outcomes in critically ill patients, such as those with sepsis or acute respiratory distress syndrome, by improving tissue perfusion (blood flow to tissues) and reducing organ injury. However, the benefits for kidney function specifically are not clearly established, and there are concerns about potential kidney damage related to albumin concentration. ^{1 2 3 4 5}

Is albumin safe for use in humans?

Human albumin solutions have been used safely for many years, with adverse events being rare. Studies show that albumin is generally safe, with low rates of mild adverse reactions, and no serious immune responses have been observed. However, some complications may occur in patients with severe injuries, and care should be taken to ensure the manufacturing process is well controlled to avoid contamination. ^{2 6 7 8 9}

How is the drug Albumin for Acute Kidney Injury different from other treatments?

Albumin for Acute Kidney Injury is unique because it uses a concentrated form of human albumin (a protein in blood plasma) to help manage fluid balance and improve kidney function, which is different from other treatments that may not use this specific protein or concentration. ^{1 2 3 7 10}

Research Team

Edward G Clark, MD MSc FRCPC

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

Adults over 18 in intensive care for more than a day, on life support or needing immediate kidney dialysis due to acute injury. Not for those with certain chronic kidney conditions, recent kidney transplants, severe liver issues, brain injuries, past severe reactions to albumin, or if they've had multiple dialysis sessions already.

Inclusion Criteria

I am about to start or continue dialysis for acute kidney injury.

I am on medication to control my blood pressure or using a machine to help me breathe.

I have been in the ICU for more than a day.

Exclusion Criteria

I have been diagnosed with end-stage kidney disease before being hospitalized.

My brain pressure is high, as shown by monitoring.

Contraindication or known objection to albumin/blood product transfusions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either albumin or normal saline boluses during RRT sessions in ICU for up to 14 days

14 days

Daily RRT sessions in ICU

Follow-up

Participants are monitored for organ support-free days and RRT-free days at 28 days following randomization

28 days

Long-term Follow-up

Participants are evaluated for health-related quality of life and RRT dependence at 90 days

90 days

Treatment Details

Interventions

• 0.9% Normal Saline
• 20-25% Albumin fluid
• Alburex 25% Albumin fluid

Trial Overview The trial is testing if giving high-concentration albumin fluid during dialysis helps critically ill patients recover organ function faster compared to normal saline. Patients are randomly chosen to receive either the albumin or saline during their treatment.

Participant Groups

Group I: 20-25% Albumin fluid Active Control 1 Intervention

100 mL 20-25% Albumin fluid at the initiation of continuous renal replacement therapy (CRRT), prolonged intermittent renal replacement therapy (PIRRT), or intermittent hemodialysis (IHD) and another 100 mL 20-25% Albumin fluid and halfway through RRT sessions in ICU.

Group II: Normal Saline Placebo Group 1 Intervention

100 mL at the initiation of CRRT, SLED or IHD and another 100 mL 0.9% Normal Saline halfway through RRT sessions in ICU.

20-25% Albumin fluid is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Albumin (Human) 20% for:

• Hypovolemia
• Hypoalbuminemia
• Prevention of central volume depletion after paracentesis due to cirrhotic ascites
• Ovarian hyperstimulation syndrome (OHSS)
• Adult respiratory distress syndrome (ARDS)
• Acute nephrosis
• Hemolytic Disease of the Newborn (HDN)

Approved in Canada as Albumin (Human) 20% for:

• Cardiac surgery
• Volume resuscitation for hypovolemia
• Cerebral ischemia / hypovolemic brain injury
• Hypoalbuminemia
• Large volume paracentesis in cirrhotic patients
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome type 1

Approved in European Union as Albumin (Human) 20% for:

• Hypovolemia
• Hypoalbuminemia
• Prevention of central volume depletion after paracentesis due to cirrhotic ascites
• Ovarian hyperstimulation syndrome (OHSS)
• Adult respiratory distress syndrome (ARDS)
• Acute nephrosis
• Hemolytic Disease of the Newborn (HDN)

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

The Physicians' Services Incorporated Foundation

Collaborator

Trials

165

Recruited

31,700+

The Kidney Foundation of Canada

Collaborator

Trials

16

Recruited

3,200+

The Ottawa Hospital Academic Medical Organization (TOHAMO) Innovation Fund Grant.

Collaborator

Trials

1

Recruited

860+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Canadian Blood Services

Collaborator

Trials

24

Recruited

39,200+

Héma-Québec

Collaborator

Trials

2

Recruited

1,800+

Héma-Québec

Collaborator

Trials

2

Recruited

1,800+

Findings from Research

In a study involving 27 male Wistar rats with induced sepsis, administration of 25% hyperoncotic albumin significantly improved hemodynamic stability, reducing hypotension and metabolic acidosis, while also enhancing tissue perfusion in the intestine and kidney.

The 25% albumin treatment also decreased markers of organ injury, such as elevated serum lactate dehydrogenase and blood urea nitrogen levels, and reduced inflammation in the lungs and intestines, indicating its potential as a therapeutic option in sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperoncotic albumin attenuates lung and intestine injuries caused by peritonitis-induced sepsis in rats. Chian, CF., Tsao, CM., Chen, SJ., et al.[2013]

In a study of 1,508 critically ill patients receiving continuous renal replacement therapy, the use of 20% human albumin solution (HAS) did not lead to higher 90-day mortality or longer recovery times compared to 4% HAS, indicating its safety in this context.

Patients receiving 20% HAS had a more negative fluid balance, suggesting it may influence fluid management, but it did not adversely affect overall outcomes compared to those receiving only 4% HAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients. O'Brien, Z., Finnis, M., Gallagher, M., et al.[2022]

The study aimed to evaluate the feasibility of using hyperoncotic albumin alongside diuretics in 46 critically ill patients with hypoalbuminemia, but it did not meet its feasibility goals, such as administering treatment to 80% of patients.

Clinical outcomes, including fluid balance and ventilator-free days, were similar between the albumin and placebo groups, suggesting that hyperoncotic albumin may not provide additional benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Furosemide and Albumin for Diuresis of Edema (FADE): A parallel-group, blinded, pilot randomized controlled trial. Oczkowski, SJW., Klotz, L., Mazzetti, I., et al.[2019]

In a study involving 24 male Wistar rats with induced acute lung injury, both 5% and 20% albumin solutions resulted in less lung injury compared to Ringer's lactate, indicating their potential benefits in managing lung conditions in critically ill patients.

However, the use of hyper-oncotic albumin (20%ALB) was associated with greater kidney damage compared to iso-oncotic albumin (5%ALB), suggesting that while albumin can help with lung injury, it may pose risks to kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of crystalloid, hyper-oncotic albumin, and iso-oncotic albumin on lung and kidney damage in experimental acute lung injury. Mendes, RS., Oliveira, MV., Padilha, GA., et al.[2020]

In a study involving 28 patients with severe sepsis and acute respiratory distress syndrome, administering 20% human albumin solution resulted in only a temporary improvement in oxygenation and hemodynamic parameters, particularly significant in patients receiving albumin alone.

Adding furosemide to the albumin treatment did not lead to a sustained improvement in oxygenation, indicating that while albumin raises plasma levels, it may not provide long-lasting benefits in these critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term effect of hyperoncotic albumin, given alone or with furosemide, on oxygenation in sepsis-induced acute respiratory distress syndrome. Kuper, M., Gunning, MP., Halder, S., et al.[2020]

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 11,512 post-surgical patients with shock, early exposure to hyperoncotic albumin was linked to a higher risk of acute kidney injury, with an odds ratio of 1.10, indicating a significant concern for nephrotoxicity.

There was no observed difference in hepatic injury, mortality, or length of ICU stay between patients treated with hyperoncotic albumin and those who were not, suggesting that while kidney risk is a concern, other organ functions may not be adversely affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute kidney injury in postoperative shock: is hyperoncotic albumin administration an unrecognized resuscitation risk factor? Udeh, CI., You, J., Wanek, MR., et al.[2022]

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 of 396 hospitalized patients receiving human albumin (HA), those treated for non-recommended indications (Gr. B) had significantly higher in-hospital survival rates (94%) compared to those treated for recommended indications (Gr. A) at 78.9%.

HA was found to be safe and effective in resolving conditions like hyponatremia and hepatic encephalopathy, even in patients without acute kidney injury or spontaneous bacterial peritonitis, suggesting its broader therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human albumin infusion is safe and effective even in patients without acute kidney injury and spontaneous bacterial peritonitis. Kulkarni, AV., Zuberi, AA., Chaitanya, K., et al.[2023]

References

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

Hyperoncotic albumin attenuates lung and intestine injuries caused by peritonitis-induced sepsis in rats. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients. [2022]

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

Furosemide and Albumin for Diuresis of Edema (FADE): A parallel-group, blinded, pilot randomized controlled trial. [2019]

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

Effects of crystalloid, hyper-oncotic albumin, and iso-oncotic albumin on lung and kidney damage in experimental acute lung injury. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The short-term effect of hyperoncotic albumin, given alone or with furosemide, on oxygenation in sepsis-induced acute respiratory distress syndrome. [2020]

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

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

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

Acute kidney injury in postoperative shock: is hyperoncotic albumin administration an unrecognized resuscitation risk factor? [2022]

8. 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]

9. France pubmed.ncbi.nlm.nih.gov

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

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

Human albumin infusion is safe and effective even in patients without acute kidney injury and spontaneous bacterial peritonitis. [2023]