Amino Acid Nutrition for Critical Illness

(AA-ICU Trial)

Overseen By Josie Campisi, RN, CRC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Arnold Kristof

Disqualifiers: Moribund, Life-sustaining withdrawal, Parenteral nutrition, Severe liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids.

Do I have to stop taking my current medications for this trial?

The trial protocol 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 safety data exists for amino acid nutrition in critical illness?

The safety data for amino acid nutrition in critical illness is limited. Some studies have reported severe side effects with parenteral nutrition containing amino acids, fat emulsion, and glucose. However, these studies primarily focus on the lipid component rather than amino acids specifically. Alternative lipid emulsions, such as olive oil-based formulations, have shown a better safety profile compared to soybean oil-based emulsions, but further research is needed to determine the safety of amino acid components in these formulations. ^{1 2 3 4 5}

Is Peptamen 1.5%, Prosol 20% IV a promising treatment for critical illness?

Yes, Peptamen 1.5%, Prosol 20% IV is a promising treatment for critical illness because it provides essential amino acids that help improve protein synthesis and energy supply, which are crucial for recovery in critically ill patients. ^{6 7 8 9 10}

What data supports the idea that Amino Acid Nutrition for Critical Illness is an effective treatment?

The available research does not provide any data specifically supporting the effectiveness of Amino Acid Nutrition for Critical Illness. The studies mentioned focus on other treatments and drugs, such as antibiotics and their dosing in critically ill children, rather than on Amino Acid Nutrition. ^{11 12 13 14 15}

Who Is on the Research Team?

Arnold S Kristof, MDCM, FRCPC

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are critically ill, on mechanical ventilation in the ICU, and expected to need intensive care for at least three more days. It's not suitable for those with conditions that might interfere with the study or pose extra risks.

Inclusion Criteria

I am an adult on a ventilator in the ICU and expected to need it or other intensive care for at least 3 more days.

Exclusion Criteria

I have a connection between my lung and chest wall.

I am not on dialysis or ECMO because they affect how my body handles proteins.

Patients who are moribund (expected death within 48 hours)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous amino acids and enteral feeding to assess protein metabolism and anabolic processes

48 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety, effectiveness, and secondary outcomes such as mortality and hospital-acquired infections

72 hours to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Peptamen 1.5%
• Prosol 20% IV

Trial Overview The study tests if giving extra amino acids through Peptamen (a nutrient mix) via a feeding tube or Prosol IV can help build up body proteins in critically ill patients better than standard care.

How Is the Trial Designed?

Group I: Group 2: Prosol 20% IV to 1.75g/kg/day Active Control 2 Interventions

Patients in group 2 will receive the same enteral feeding as group 1 (Peptamen 1.5) but in addition will receive sufficient intravenous amino acid supplements (Prosol 20%) to achieve an effective fixed dose of 1.75 g/kg/d

Group II: Group 3: Prosol 20% IV to 2.5g/kg/day Active Control 2 Interventions

Patients in this group will receive intravenous amino acids (Prosol 20%) in addition to standard enteral Peptamen 1.5% to achieve an effective protein intake of 2.5 g/kg/day.

Group III: Group 1: Peptamen 1.5% via enteral only Active Control 1 Intervention

Study patients in this group will be prescribed 1.0 g/kg/d of protein using standard EN Peptamen 1.5%. Based on current compliance or tolerance statistics, investigators expect patients to only receive 50-60% of these prescribed doses; effective protein intake will therefore be approximately 0.5-0.6 g/kg/d

Peptamen 1.5% is already approved in United States, European Union for the following indications:

Approved in United States as Peptamen 1.5 for:

• Malabsorption
• Short bowel syndrome
• Chronic diarrhea
• Cystic fibrosis
• Malnutrition
• Cerebral palsy
• Crohn's disease

Approved in European Union as Peptamen 1.5 for:

• Impaired GI function
• Malabsorption
• Short bowel syndrome
• Chronic diarrhea
• Cystic fibrosis
• Malnutrition
• Cerebral palsy
• Crohn's disease

Who Is Running the Clinical Trial?

Arnold Kristof

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Using an individualized pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass resulted in a significantly lower protamine requirement compared to a fixed-dose model, with patients needing an average of 243 mg versus 305 mg (p<0.001).

The algorithm did not negatively impact clotting times or transfusion requirements, suggesting it is a safe and effective alternative to traditional dosing methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass. Miles, LF., Marchiori, P., Falter, F.[2018]

Continuous infusion (CI) of beta-lactam antibiotics in critically ill children resulted in a higher likelihood of achieving optimal pharmacokinetic exposure compared to intermittent infusion (II), with 69% of CI patients meeting the target versus 47% of II patients.

While CI improved the chances of optimal exposure, it also increased the risk of overexposure, highlighting the need for regular therapeutic drug monitoring in these patients to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-lactam exposure and safety in intermittent or continuous infusion in critically ill children: an observational monocenter study. Debray, A., Callot, D., Hirt, D., et al.[2023]

In a study of 28 critically ill children receiving continuous vancomycin infusion, the current dosing scheme was found to be inadequate, leading to underexposure in many patients, with 25% exceeding the recommended area under the curve for effective treatment.

The use of pharmacokinetic models to adjust initial dosing based on individual patient factors like age and weight could improve vancomycin therapy effectiveness, aiming for better target attainment in plasma concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children. Genuini, M., Oualha, M., Bouazza, N., et al.[2019]

In a study of 9 critically ill children receiving continuous renal replacement therapy, the standard meropenem dosing of 40 mg/kg every 12 hours was found to achieve the desired antibiotic concentration in only 32% of cases.

Alternative dosing regimens of 20 mg/kg every 8 hours over 4 hours or 40 mg/kg every 8 hours over 2 hours successfully met the pharmacokinetic/pharmacodynamic target for 90% of patients, indicating these may be more effective dosing strategies for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. Tan, WW., Watt, KM., Boakye-Agyeman, F., et al.[2023]

A review of 21 studies on beta-lactam antibiotics in septic pediatric patients highlights the importance of individualized antimicrobial therapy based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to effectively treat life-threatening infections.

Strategies such as prolonging infusion times and increasing frequency of administration were commonly used to enhance the effectiveness of beta-lactams, suggesting that therapeutic monitoring could improve treatment outcomes in septic children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-Lactams Therapeutic Monitoring in Septic Children-What Target Are We Aiming for? A Scoping Review. Morales Junior, R., Pereira, GO., Tiguman, GMB., et al.[2022]

In critically ill children requiring parenteral nutrition, soybean oil lipid injectable emulsion (SO-ILE) was linked to a higher incidence of hypertriglyceridemia (HTG) and elevated inflammatory markers compared to a mixed lipid emulsion (SO,MCT,OO,FO-ILE).

The study found that the mortality rate was significantly higher in the SO-ILE group, with an adjusted odds ratio of 2.3, indicating a potential safety concern with this lipid formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SO,MCT,OO,FO-ILE Is Associated With Better Side Effect Profile Than SO-ILE in Critically Ill Children Receiving Parenteral Nutrition. Gupta, N., Ali, C., Talathi, S.[2023]

Two patients with advanced tumors experienced severe adverse reactions after receiving parenteral nutrition containing fat emulsion (10%)/amino acids (15)/glucose (20%), highlighting potential safety concerns with this nutritional support.

Despite the adverse reactions, symptoms were relieved upon stopping the infusion, and the patients did not experience similar side effects upon re-administration, suggesting that careful monitoring and individualized administration plans are crucial for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe side effects caused by parenteral nutrition therapy with fat emulsion (10%)/amino acids (15)/glucose (20%) injection: 2 case reports. Jia, H., Sun, Y., Hou, F., et al.[2022]

Alternative intravenous fat emulsions (IVFEs) like medium-chain triglycerides, olive oils, and fish oils may offer similar safety profiles to standard soybean oil-based IVFEs, but they are not yet available in the U.S.

These alternative IVFEs could potentially improve clinical outcomes for patients in compromised states by reducing the intake of proinflammatory ω-6 fatty acids found in soybean oil, suggesting a need for further research on their efficacy and optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. Vanek, VW., Seidner, DL., Allen, P., et al.[2015]

In a study involving 458 hospitalized adult patients, olive-oil-based three-chamber bags (3CBs) for parenteral nutrition were found to be non-inferior to soybean-oil-based compounded bags (CoBs) in terms of efficacy, as measured by serum prealbumin levels after 5 days.

The olive-oil-based 3CBs were not only well tolerated but also associated with a significantly lower infection rate compared to the soybean-based CoBs, suggesting a potential safety advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition. Jia, Z., Yang, J., Qin, H.[2022]

In a study involving 78 critically ill neonates, an olive oil-based lipid emulsion (ClinOleic) was found to be well tolerated with no adverse events, indicating its safety for use in this vulnerable population.

After 5 days of treatment, the olive oil emulsion significantly increased plasma levels of oleic acid compared to a soybean oil emulsion, while also showing a lower increase in linoleic acid, reflecting the different fatty acid compositions of the emulsions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial. Webb, AN., Hardy, P., Peterkin, M., et al.[2015]

In critical illness, skeletal muscle undergoes adaptations that can lead to insulin resistance and muscle wasting, making adequate protein and amino acid nutrition essential for recovery, with optimal intake levels suggested to be between 1.3 and 1.5 g/kg/day.

Anabolic resistance in critically ill patients reduces the effectiveness of protein intake, highlighting the importance of mobility protocols in intensive care to enhance nutritional interventions and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein metabolism and requirements. Biolo, G.[2019]

Amino acid-based nutritional support is important for improving nitrogen balance in critically ill, catabolic patients, but the optimal composition of amino acids is still being defined.

The review highlights the significance of conditionally indispensable amino acids and suggests specific amino acids like histidine, serine, and glutamine, as well as the potential benefits of using dipeptides for parenteral nutrition in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are intravenous amino acid solutions unbalanced? Fürst, P., Stehle, P.[2005]

In a study of 119 critically ill patients receiving parenteral nutrition, those given a higher amino acid intake of 1.2 g/kg showed improved handgrip strength and reduced fatigue compared to those receiving 0.8 g/kg, although grip strength at ICU discharge was not significantly different overall.

The higher amino acid intake also resulted in greater muscle thickness and better nitrogen balance early in the treatment, supporting the recommendation for increased protein provision in ICU patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Requirements in the Critically Ill: A Randomized Controlled Trial Using Parenteral Nutrition. Ferrie, S., Allman-Farinelli, M., Daley, M., et al.[2022]

Early enteral nutrition after major rectal surgery led to better clinical outcomes, such as reduced postoperative ileus and shorter hospital stays, compared to early parenteral nutrition in a study of 123 patients.

Despite lower plasma concentrations of glutamine and arginine in the enteral nutrition group, these amino acid levels did not explain the improved recovery outcomes, suggesting that the benefits of early enteral feeding are not directly linked to plasma amino acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial. van Barneveld, KW., Smeets, BJ., Heesakkers, FF., et al.[2017]

For adult patients receiving parenteral nutrition (PN), a general amino acid intake of 0.8 g/kg/day is recommended, which can be increased to 1.2-1.5 g/kg/day in normal conditions and up to 2.0-2.5 g/kg/day in exceptional cases, ensuring adequate protein synthesis and reduced catabolism.

In critically ill patients, glutamine should be administered parenterally if indicated, while specific amino acid solutions, such as those with branched-chain amino acids, are recommended for treating hepatic encephalopathy, but not for other conditions like acute pancreatitis or after bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acids - Guidelines on Parenteral Nutrition, Chapter 4. Stein, J., Boehles, HJ., Blumenstein, I., et al.[2021]

Citations

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

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Beta-lactam exposure and safety in intermittent or continuous infusion in critically ill children: an observational monocenter study. [2023]

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

Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children. [2019]

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

Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Beta-Lactams Therapeutic Monitoring in Septic Children-What Target Are We Aiming for? A Scoping Review. [2022]

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

SO,MCT,OO,FO-ILE Is Associated With Better Side Effect Profile Than SO-ILE in Critically Ill Children Receiving Parenteral Nutrition. [2023]

7. China pubmed.ncbi.nlm.nih.gov

Severe side effects caused by parenteral nutrition therapy with fat emulsion (10%)/amino acids (15)/glucose (20%) injection: 2 case reports. [2022]

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

A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. [2015]

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

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition. [2022]

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

Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial. [2015]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Protein metabolism and requirements. [2019]

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

Are intravenous amino acid solutions unbalanced? [2005]

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

Protein Requirements in the Critically Ill: A Randomized Controlled Trial Using Parenteral Nutrition. [2022]

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

Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial. [2017]

15. Germany pubmed.ncbi.nlm.nih.gov

Amino acids - Guidelines on Parenteral Nutrition, Chapter 4. [2021]