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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT01206166
First received: September 14, 2010
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • Amount of calories and protein received [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • 60 day mortality [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ICU mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Development of ICU-acquired infections [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Hospital mortality [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Duration of ICU stay [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Multiple organ dysfunction (SOFA and PODS) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Sequential Organ Failure Assessment(SOFA) Persistent Organ Dysfunction Score (PODS)

  • Duration of mechanical ventilation [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • SF36 [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    Survival and health-related quality of life

  • Duration of hospital stay [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Muscle Function - Ultrasounds [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Ultrasounds of the femoral quadriceps will be done to assess the muscle layer thickness (MLT) of the M. vastus intermedius and M rectus femoris.

  • Muscle Function - CT Scans [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    CT scans done for clinical reasons done at the 3rd lumbar vertebrae will be used to assess muscle mass.

  • Muscle Function - Hand-Grip Strength [ Time Frame: ICU Discharge ] [ Designated as safety issue: No ]
    At ICU discharge, a hand-grip strength test will be done.

  • Muscle Function - 6 min walk test [ Time Frame: ICU Discharge ] [ Designated as safety issue: No ]
    At ICU discharge, a 6 min walk test will be done.


Estimated Enrollment: 160
Study Start Date: June 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enteral Nutrition plus 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.
No Intervention: Enteral Nutrition Only

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01206166

Contacts
Contact: Rupinder Dhaliwal 613-549-6666 ext 3830 dhaliwar@kgh.kari.net

Locations
United States, Colorado
University of Colorado DHSC Recruiting
Boulder, Colorado, United States, 80045
Contact: Paul Wischmeyer, MD       Paul.Wischmeyer@ucdenver.edu   
United States, Missouri
Mercy Hospital St. Louis Recruiting
St. Louis, Missouri, United States, 63141
Contact: Rekha Lakshmanan       Rekha.Lakshmanan@Mercy.Net   
Washington University School of Medicine in St. Louis Recruiting
St. Louis, Missouri, United States, 63110-1093
Contact: Grant Bochicchio       bochicchiog@wudosis.wustl.edu   
United States, Ohio
Cleveland Clinic Lerner College of Medicine Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Ellen Wurm       WURME@ccf.org   
The Ohio State Univsersity Medical Center Recruiting
Columbus, Ohio, United States, 43221
Contact: Beth Besecker       Beth.Besecker@osumc.edu   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Bob Martindale       martindr@ohsu.edu   
United States, Texas
University of Texas Health Science Center Recruiting
Houston, Texas, United States, 77030
Contact: Rosemary Kozar       Rosemary.A.Kozar@uth.tmc.edu   
Belgium
Erasme University Hospital Active, not recruiting
Brussels, Belgium, B - 1070
Canada, Alberta
Royal Alexandra Hospital Active, not recruiting
Edmonton, Alberta, Canada, T5H 3V9
University of Alberta Active, not recruiting
Edmonton, Alberta, Canada, T5H 3V9
Grey Nuns Hospital Active, not recruiting
Edmonton, Alberta, Canada, T6L 5X8
France
Nouvel Hôpital Civil Active, not recruiting
Strasbourg, France, F - 67091
Sponsors and Collaborators
Clinical Evaluation Research Unit at Kingston General Hospital
Baxter Healthcare Corporation
Investigators
Study Chair: Daren K. Heyland, MD Clinical Evaluation Research Unit, Kingston General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT01206166     History of Changes
Other Study ID Numbers: TOP-UP
Study First Received: September 14, 2010
Last Updated: July 3, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Direction Générale de la Santé

Keywords provided by 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:
Critical Illness
Respiratory Insufficiency
Respiratory Distress Syndrome, Adult
Disease Attributes
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Lung Diseases

ClinicalTrials.gov processed this record on September 30, 2014