Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP)

Study Overview
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Brief Summary
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The specific aim of the proposed study is to conduct a pilot study involving 160 critically-ill lean and obese patients enrolled at 11 sites in Canada, the United States of America, Belgium and France in order to: Specific Aims Confirm that we can achieve a clinically significant difference in calorie and protein intake between the two intervention groups. Estimate recruitment rate i.e. number of eligible and enrolled patients per month per site. Evaluate the safety, tolerance, and logistics around providing supplemental PN in the study population in the context of a multicenter trial, e.g. To ensure adequate glycemic control in both groups. To ensure that the other metabolic consequences of the feeding strategies are minimized. To establish adequate compliance with study protocols and completion of case report forms A secondary aim of this pilot study will be: • To explore the effect of differential effects of calorie and protein delivery on muscle and mass function.

Detailed Description
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Background Critically ill patients are often hypermetabolic and can rapidly become nutritionally compromised. Malnutrition is prevalent in these patients and has been associated with increased morbidity and mortality. Standard nutrition therapy, i.e. provision of calories, protein and other nutrients consists primarily of enteral nutrition (via a feeding tube into the gastrointestinal tract), parenteral nutrition (via an intravenous tube into the blood), or occasionally a combination of both. However, the provision of nutrition is sub-optimal and the majority of critically-ill patients do not meet nutritional requirements. Recent studies report that average energy intakes of critically ill patients are only 49% to 70% of calculated requirements. Despite repeated, sustained efforts over the past few years, the investigators have not significantly improved the amount of calories delivered via the enteral route. This leads us to conclude that if the investigators are to be successful at increasing the provision of calories and protein to patients at-risk, the investigators will have to supplement the calories via the parenteral route. Critically ill patients that are at extremes of weight are at a higher nutritional risk and have higher mortality rates. A recent International multicenter observational study of 2772 ICU patients from 165 ICUs showed a significant inverse linear relationship between the odds of mortality and total daily calories received. Increased amounts of calories was most important for the BMI < 20 group followed by the BMI 20 -< 25 group and BMI > 35 group with no benefit of increased calorie intake for patients in the BMI 25 -< 35 group. Feeding an additional 1000 kcals almost halved the odds of 60-day mortality in patients with a BMI < 25 or > 35. Similar results were observed for feeding an additional 30 grams of protein per day. Thus, a prospective randomized trial is warranted to confirm our hypothesis that in patients with a BMI of < 25 and those with a BMI > 35 increasing the provision of more energy and protein can impact clinical outcomes. The results of this study will serve to answer some fundamental questions with regards to impact of amount of energy and protein delivered to nutritional at-risk ICU patients and will inform current practice. Study Intervention: Patients will be randomized to one of 2 interventions: enteral nutrition alone or enteral nutrition plus parenteral nutrition (supplemental PN group).

Official Title
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A Randomized Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients: The TOP UP Trial (Pilot)

Conditions
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Critical Illness, Acute Respiratory Failure

Intervention / Treatment
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* Drug: Olimel (5.7%E / N9E)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill adult patient (≥ 18 years) admitted to ICU Has acute respiratory failure (ARF) i.e. expected to remain mechanically ventilated for more than 48 hours Expected ICU dependency of 5 or more days On or expected to initiate enteral nutrition within 7 days of ICU admission BMI <25 or ≥ 35 based on pre-ICU actual or estimated dry weight Exclusion Criteria: >72 hours from admission to ICU to time of consent Not expected to survive an additional 48 hrs from screening evaluation A lack of commitment to full aggressive care (anticipated withholding or withdrawing treatments in the first week but isolated DNR acceptable) Patients already receiving PN at screening Absence of All gastrointestinal risk factors, defined as: High Apache II Score (>20) On more than 1 vasopressor or increasing doses or vasopressors Receiving continuous infusion of narcotics High nasogastric/orogastric output (>500 mL over 24 hours) Recent surgery involving esophagus, stomach, or small bowel OR peritoneal contamination with bowel contents Pancreatitis Multiple gastrointestinal investigations Recent history of diarrhea/C. Difficile Surgical patients with future surgeries planned Ruptured or dissected abdominal aortic aneurysm Patients admitted with diabetic ketoacidosis or non-ketotic hyperosmolar coma Pregnant or lactating patients Patients with clinical fulminant hepatic failure Patients with Cirrhosis Child's Class C Liver Disease (except those on a transplant list or transplantable) Dedicated port of central line not available Known allergy to study nutrients (soy, eggs or olive products) Enrolment in another industry sponsored ICU intervention study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enteral Nutrition + Parenteral Nutrition<br>Enteral nutrition with the addition of parenteral supplementation (Olimel 5.7%E/N9E). | Drug: Olimel (5.7%E / N9E)<br>* OLIMEL(Amino Acids, Dextrose, Lipids, with / without Electrolytes) is indicated for parenteral nutrition for adults when oral or enteral nutrition is impossible, insufficient or contraindicated.<br>* Other names: Olimel;|
| No Intervention: Enteral Nutrition Only<br>Enteral nutrition only - no intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calorie & Protein Intake 7 Days Post Randomization | Amount of calories & protein received as a percentage of prescribed. | 7 days post randomization | 
| Calorie & Protein Intake in First 27 Days | Amount of calories & protein received as a percentage of prescribed. | first 27 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Month Mortality | Kaplan-Meier estimate. | 6 months | 
| ICU Mortality |  | 6 months | 
| Hospital Mortality |  | 6 months | 
| Duration of ICU Stay |  | 6 months | 
| Duration of Hospital Stay |  | 6 months | 
| Duration of Mechanical Ventilation |  | 6 months | 
| Development of ICU-acquired Infections |  | ICU discharge | 
| SF36-Physical Functioning Domain | The SF-36 physical function domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF-36 Physical Functioning Domain | The SF-36 physical function domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| Functional Status at Hospital Discharge |  | hospital discharge | 
| SF36 Role Physical Domain | The SF-36 role physical function domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Pain Index Domain | The SF-36 pain index domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 General Health Perceptions Domain | The SF-36 general health perceptions domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Vitality Domain | The SF-36 vitality domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Social Functioning Domain | The SF-36 social functioning domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Role-emotional Domain | The SF-36 role-emotion domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Mental Health Index Domain | The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome. | 3 months | 
| SF36 Standardized Physical Component Scale | The SF36 Standardized Physical Component Scale has been scaled to have a mean of zero and standard deviation of 10 in a general US population. Higher scores indicate better HRQoL. | 3 months | 
| SF36 Standardized Mental Component Scale | The SF36 Standardized Mental Component Scale has been scaled to have a mean of zero and standard deviation of 10 in a general US population. Higher scores indicate better HRQoL. | 3 months | 
| SF-36 Role-physical Domain | The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Pain Index Domain | The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 General Health Perceptions Domain | The SF-36 general health perceptions domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Vitality Domain | The SF-36 vitality domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Social Functioning Domain | The SF-36 social functioning domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Role-emotional Domain | The SF-36 role-emotional domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Mental Health Index Domain | The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome. | 6 months | 
| SF-36 Standardized Physical Component Scale | The SF36 Standardized Physical Component Scale has been scaled to have a mean of zero and standard deviation of 10 in a general US population. Higher scores indicate better HRQoL. | 6 months | 
| SF-36 Standardized Mental Component Scale | The SF36 Standardized mental Component Scale has been scaled to have a mean of zero and standard deviation of 10 in a general US population. Higher scores indicate better HRQoL. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized trial, Parental nutrition, Enteral nutrition, Intensive care unit, BMI < 25 or ≥ 35