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

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

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.

Study Overview

• Status: Terminated
• Conditions: Critical Illness; Acute Respiratory Failure
• Intervention / Treatment: Drug: Olimel (5.7%E / N9E)

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).

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B - 1070
    • Erasme University Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandra Hospital
    • Edmonton, Alberta, Canada, T6L 5X8
      • Grey Nuns Hospital
    • Edmonton, Alberta, Canada, T5H 3V9
      • University of Alberta
• France
  • Strasbourg, France, F - 67091
    • Nouvel Hopital Civil
• United States
  • Colorado
    • Boulder, Colorado, United States, 80045
      • University of Colorado DHSC
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital St. Louis
    • Saint Louis, Missouri, United States, 63110-1093
      • Washington University School of Medicine in St. Louis
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Lerner College of Medicine
    • Columbus, Ohio, United States, 43221
      • The Ohio State Univsersity Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteral Nutrition + Parenteral Nutrition; Enteral nutrition with the addition of parenteral supplementation (Olimel 5.7%E/N9E).	Drug: Olimel (5.7%E / N9E); 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.; Other Names: Olimel
No Intervention: Enteral Nutrition Only; Enteral nutrition only - no intervention

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
• Collaborators: Baxter Healthcare Corporation
• Investigators: Study Chair: Daren K. Heyland, MD, Clinical Evaluation Research Unit, Kingston General Hospital

Publications and helpful links

General Publications

• Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R, Heyland DK. The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med. 2009 Oct;35(10):1728-37. doi: 10.1007/s00134-009-1567-4. Epub 2009 Jul 2. Erratum In: Intensive Care Med. 2009 Oct;35(10):1821.
• Villet S, Chiolero RL, Bollmann MD, Revelly JP, Cayeux R N MC, Delarue J, Berger MM. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr. 2005 Aug;24(4):502-9. doi: 10.1016/j.clnu.2005.03.006.
• Krishnan JA, Parce PB, Martinez A, Diette GB, Brower RG. Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes. Chest. 2003 Jul;124(1):297-305. doi: 10.1378/chest.124.1.297.
• Hise ME, Halterman K, Gajewski BJ, Parkhurst M, Moncure M, Brown JC. Feeding practices of severely ill intensive care unit patients: an evaluation of energy sources and clinical outcomes. J Am Diet Assoc. 2007 Mar;107(3):458-65. doi: 10.1016/j.jada.2006.12.012.
• Dhaliwal R, Jurewitsch B, Harrietha D, Heyland DK. Combination enteral and parenteral nutrition in critically ill patients: harmful or beneficial? A systematic review of the evidence. Intensive Care Med. 2004 Aug;30(8):1666-71. doi: 10.1007/s00134-004-2345-y. Epub 2004 Jun 8.
• Wischmeyer PE, Hasselmann M, Kummerlen C, Kozar R, Kutsogiannis DJ, Karvellas CJ, Besecker B, Evans DK, Preiser JC, Gramlich L, Jeejeebhoy K, Dhaliwal R, Jiang X, Day AG, Heyland DK. A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial. Crit Care. 2017 Jun 9;21(1):142. doi: 10.1186/s13054-017-1736-8.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 14, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Intensive care unit; Randomized trial; Enteral nutrition; Parental nutrition; BMI < 25 or ≥ 35
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Disease Attributes; Body Weight; Respiratory Insufficiency; Overweight; Critical Illness
• Other Study ID Numbers: TOP-UP