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

Phase 3
Terminated
Conditions
Critical Illness
Acute Respiratory Failure
Interventions
Registration Number
NCT01206166
Lead Sponsor
Clinical Evaluation Research Unit at Kingston General Hospital
Brief Summary

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

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).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
125
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:

    1. High Apache II Score (>20)
    2. On more than 1 vasopressor or increasing doses or vasopressors
    3. Receiving continuous infusion of narcotics
    4. High nasogastric/orogastric output (>500 mL over 24 hours)
    5. Recent surgery involving esophagus, stomach, or small bowel OR peritoneal contamination with bowel contents
    6. Pancreatitis
    7. Multiple gastrointestinal investigations
    8. Recent history of diarrhea/C. Difficile
    9. Surgical patients with future surgeries planned
    10. 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Enteral Nutrition + Parenteral NutritionOlimel (5.7%E / N9E)Enteral nutrition with the addition of parenteral supplementation (Olimel 5.7%E/N9E).
Primary Outcome Measures
NameTimeMethod
Calorie & Protein Intake 7 Days Post Randomization7 days post randomization

Amount of calories \& protein received as a percentage of prescribed.

Calorie & Protein Intake in First 27 Daysfirst 27 days

Amount of calories \& protein received as a percentage of prescribed.

Secondary Outcome Measures
NameTimeMethod
Development of ICU-acquired InfectionsICU discharge
Hospital Mortality6 months
Duration of Hospital Stay6 months
SF-36 Vitality Domain6 months

The SF-36 vitality domain ranges from 0-100. Higher scores indicate better outcome.

ICU Mortality6 months
Duration of ICU Stay6 months
SF36-Physical Functioning Domain3 months

The SF-36 physical function domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 Physical Functioning Domain6 months

The SF-36 physical function domain ranges from 0-100. Higher scores indicate better outcome.

Functional Status at Hospital Dischargehospital discharge
SF36 Pain Index Domain3 months

The SF-36 pain index domain ranges from 0-100. Higher scores indicate better outcome.

SF36 General Health Perceptions Domain3 months

The SF-36 general health perceptions domain ranges from 0-100. Higher scores indicate better outcome.

SF36 Social Functioning Domain3 months

The SF-36 social functioning domain ranges from 0-100. Higher scores indicate better outcome.

SF36 Role-emotional Domain3 months

The SF-36 role-emotion domain ranges from 0-100. Higher scores indicate better outcome.

SF36 Mental Health Index Domain3 months

The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome.

Duration of Mechanical Ventilation6 months
SF36 Standardized Physical Component Scale3 months

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.

SF-36 Pain Index Domain6 months

The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome.

6 Month Mortality6 months

Kaplan-Meier estimate.

SF36 Standardized Mental Component Scale3 months

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.

SF-36 Role-physical Domain6 months

The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 General Health Perceptions Domain6 months

The SF-36 general health perceptions domain ranges from 0-100. Higher scores indicate better outcome.

SF36 Role Physical Domain3 months

The SF-36 role physical function domain ranges from 0-100. Higher scores indicate better outcome.

SF36 Vitality Domain3 months

The SF-36 vitality domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 Role-emotional Domain6 months

The SF-36 role-emotional domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 Mental Health Index Domain6 months

The SF-36 mental health index domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 Social Functioning Domain6 months

The SF-36 social functioning domain ranges from 0-100. Higher scores indicate better outcome.

SF-36 Standardized Physical Component Scale6 months

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.

SF-36 Standardized Mental Component Scale6 months

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.

Trial Locations

Locations (12)

Mercy Hospital St. Louis

🇺🇸

Saint Louis, Missouri, United States

The Ohio State Univsersity Medical Center

🇺🇸

Columbus, Ohio, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Cleveland Clinic Lerner College of Medicine

🇺🇸

Cleveland, Ohio, United States

Grey Nuns Hospital

🇨🇦

Edmonton, Alberta, Canada

Nouvel Hôpital Civil

🇫🇷

Strasbourg, France

University of Colorado DHSC

🇺🇸

Boulder, Colorado, United States

University of Texas Health Science Center

🇺🇸

Houston, Texas, United States

Washington University School of Medicine in St. Louis

🇺🇸

Saint Louis, Missouri, United States

Royal Alexandra Hospital

🇨🇦

Edmonton, Alberta, Canada

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Erasme University Hospital

🇧🇪

Brussels, Belgium

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