Albumin for Acute Kidney Injury

(ALTER-AKI Trial)

Recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intravenous albumin (a protein solution) benefits ICU patients with serious kidney problems requiring dialysis (a blood-cleaning process). The researchers aim to determine if albumin can increase the number of days patients spend without needing organ support or dialysis over 28 days. Participants will be randomly assigned to receive either the albumin treatment or normal saline (a saltwater solution) for comparison. Suitable candidates have been in the ICU for more than a day, need assistance with breathing or blood pressure, and are about to start or continue dialysis for acute kidney injury. As a Phase 4 trial, this research examines how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for the treatments in this trial?

Research has shown that the type of albumin used in this trial can be safely administered to patients who might develop kidney problems after blood transfusions. However, one study found that using 20% albumin post-surgery could increase the risk of kidney issues, especially in patients with pre-existing kidney problems. In other cases, researchers found it unclear whether albumin fluids pose more risk to the kidneys compared to other fluids like starches.

Overall, the evidence on safety is mixed. Some studies suggest it is safe, while others highlight potential risks, particularly for individuals with existing kidney concerns. This treatment is being tested in a late-stage trial, which usually indicates some previous data on safety. However, results can vary in different situations. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Albumin fluid is unique because it provides a concentrated 20-25% solution that can be crucial for patients with acute kidney injury needing renal replacement therapy. Unlike the standard of care, which often involves normal saline, albumin fluid offers potential benefits in maintaining blood volume and pressure more effectively. Researchers are excited about this treatment because it might improve outcomes for patients in critical care settings by enhancing fluid balance and supporting kidney function during therapy.

What evidence suggests that 20-25% Albumin fluid might be an effective treatment for Acute Kidney Injury?

Research has shown that hyperoncotic albumin can significantly reduce the risk of sudden kidney problems by 76% and lower the risk of death by 48%. In this trial, participants may receive 20-25% Albumin fluid, a form of hyperoncotic albumin. Studies have found this type of albumin to be more effective for patients compared to other forms. Previous research suggests that hyperoncotic albumin can be safely used in patients at risk of developing kidney issues. This makes it a promising option for those who may need kidney support, as it could help increase the number of days without needing organ support. Another group in this trial will receive Normal Saline as a comparator. ^{3 4 6 7 8}

Who Is on the Research Team?

Edward G Clark, MD MSc FRCPC

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4256900/

Albumin administration is associated with acute kidney injury ... Study results regarding administration of albumin-containing fluids have been conflicting. Hyperoncotic albumin has demonstrated a clear benefit in patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04705896

Albumin To Enhance Recovery After Acute Kidney Injury 20-25% Albumin fluid. 100 mL 20-25% Albumin fluid at the initiation of continuous renal replacement therapy (CRRT), prolonged intermittent renal replacement ...

3. journal.chestnet.org journal.chestnet.org/article/S0012-3692(24)05315-7/abstract

Comparative Effectiveness of Albumin vs No ... - CHEST Journal There was no significant difference with 5% albumin (OR, 1.07; 95% CI, 0.84-1.37), but there was a significantly increased risk with 25% albumin ...

4. mdpi.com mdpi.com/1422-0067/24/3/2333

Association between 20% Albumin Use and Acute Kidney ... Our findings suggest that hyper-oncotic albumin can be safely administered to patients who are at risk of developing AKI due to RBC transfusion.

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/cc9308

Hyperoncotic colloids and acute kidney injury: a meta-analysis ... Hyperoncotic albumin decreased the odds of acute kidney injury by 76% and of death by 48%. Hyperoncotic hydroxyethyl starch increased the odds ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9916446/

Association between 20% Albumin Use and Acute Kidney ... Our findings suggest that hyper-oncotic albumin can be safely administered to patients who are at risk of developing AKI due to RBC transfusion.

7. jamanetwork.com jamanetwork.com/journals/jamasurgery/article-abstract/2835041

Postoperative 20% Albumin Infusion and Acute Kidney ... In this study, a postoperative 20% albumin infusion increased the risk of AKI, an effect that was more pronounced in patients with a preoperative estimated ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1053077024010176

The Renal Effect of 20% Human Albumin Solution Fluid ... FBT with 20% albumin compared with crystalloid-based regimen did not reduce the occurrence of AKI in patients after cardiac surgery.