Working… Menu
Help guide our efforts to modernize
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01206166
Recruitment Status : Terminated (Low enrollment rates.)
First Posted : September 21, 2010
Last Update Posted : April 5, 2017
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Daren K. Heyland, 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.

Condition or disease Intervention/treatment Phase
Critical Illness Acute Respiratory Failure Drug: Olimel (5.7%E / N9E) Phase 3

Detailed Description:


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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Randomized Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients: The TOP UP Trial (Pilot)
Study Start Date : June 2011
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

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 Name: Olimel

No Intervention: Enteral Nutrition Only
Enteral nutrition only - no intervention

Primary Outcome Measures :
  1. Amount of calories and protein received [ Time Frame: 28 days ]
  2. 60 day mortality [ Time Frame: 60 days ]

Secondary Outcome Measures :
  1. ICU mortality [ Time Frame: 28 days ]
  2. Development of ICU-acquired infections [ Time Frame: 28 days ]
  3. Hospital mortality [ Time Frame: 60 days ]
  4. Duration of ICU stay [ Time Frame: 60 days ]
  5. Multiple organ dysfunction (SOFA and PODS) [ Time Frame: 28 days ]
    Sequential Organ Failure Assessment(SOFA) Persistent Organ Dysfunction Score (PODS)

  6. Duration of mechanical ventilation [ Time Frame: 28 days ]
  7. SF36 [ Time Frame: 60 days ]
    Survival and health-related quality of life

  8. Duration of hospital stay [ Time Frame: 60 days ]
  9. Muscle Function - Ultrasounds [ Time Frame: 28 days ]
    Ultrasounds of the femoral quadriceps will be done to assess the muscle layer thickness (MLT) of the M. vastus intermedius and M rectus femoris.

  10. Muscle Function - CT Scans [ Time Frame: 28 days ]
    CT scans done for clinical reasons done at the 3rd lumbar vertebrae will be used to assess muscle mass.

  11. Muscle Function - Hand-Grip Strength [ Time Frame: ICU Discharge ]
    At ICU discharge, a hand-grip strength test will be done.

  12. Muscle Function - 6 min walk test [ Time Frame: ICU Discharge ]
    At ICU discharge, a 6 min walk test will be done.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01206166

Layout table for location information
United States, Colorado
University of Colorado DHSC
Boulder, Colorado, United States, 80045
United States, Missouri
Washington University School of Medicine in St. Louis
St. Louis, Missouri, United States, 63110-1093
Mercy Hospital St. Louis
St. Louis, Missouri, United States, 63141
United States, Ohio
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, United States, 44195
The Ohio State Univsersity Medical Center
Columbus, Ohio, United States, 43221
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Texas
University of Texas Health Science Center
Houston, Texas, United States, 77030
Erasme University Hospital
Brussels, Belgium, B - 1070
Canada, Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
University of Alberta
Edmonton, Alberta, Canada, T5H 3V9
Grey Nuns Hospital
Edmonton, Alberta, Canada, T6L 5X8
Nouvel Hôpital Civil
Strasbourg, France, F - 67091
Sponsors and Collaborators
Clinical Evaluation Research Unit at Kingston General Hospital
Baxter Healthcare Corporation
Layout table for investigator information
Study Chair: Daren K. Heyland, MD Clinical Evaluation Research Unit, Kingston General Hospital

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit at Kingston General Hospital Identifier: NCT01206166    
Other Study ID Numbers: TOP-UP
First Posted: September 21, 2010    Key Record Dates
Last Update Posted: April 5, 2017
Last Verified: April 2017
Keywords provided by Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital:
Randomized trial
Parental nutrition
Enteral nutrition
Intensive care unit
BMI < 25 or ≥ 35
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Insufficiency
Critical Illness
Disease Attributes
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Body Weight
Signs and Symptoms