Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP)
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:
- 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.
Acute Respiratory Failure
Drug: Olimel (5.7%E / N9E)
|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)|
- 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 ]
- 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.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
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|
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.
Patients will be randomized to one of 2 interventions: enteral nutrition alone or enteral nutrition plus parenteral nutrition (supplemental PN group).
|Contact: Rupinder Dhaliwal||613-549-6666 ext firstname.lastname@example.org|
|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||Not yet recruiting|
|St. Louis, Missouri, United States, 63141|
|Contact: Rekha Lakshmanan Rekha.Lakshmanan@Mercy.Net|
|Washington University School of Medicine in St. Louis||Not yet recruiting|
|St. Louis, Missouri, United States, 63110-1093|
|Contact: Grant Bochicchio email@example.com|
|United States, Ohio|
|The Ohio State Univsersity Medical Center||Not yet recruiting|
|Columbus, Ohio, United States, 43221|
|Contact: Beth Besecker Beth.Besecker@osumc.edu|
|United States, Oregon|
|Oregon Health & Science University||Not yet recruiting|
|Portland, Oregon, United States, 97239-3098|
|Contact: Bob Martindale firstname.lastname@example.org|
|United States, Texas|
|University of Texas Health Science Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Rosemary Kozar Rosemary.A.Kozar@uth.tmc.edu|
|Erasme University Hospital||Recruiting|
|Brussels, Belgium, B - 1070|
|Contact: Jean-Charles Preiser, MD Jean-Charles.Preiser@erasme.ulb.ac.be|
|Royal Alexandra Hospital||Recruiting|
|Edmonton, Alberta, Canada, T5H 3V9|
|Contact: Jim Kutsogiannis, MD email@example.com|
|University of Alberta||Recruiting|
|Edmonton, Alberta, Canada, T5H 3V9|
|Contact: Constantine D Karvellas, MD firstname.lastname@example.org|
|Grey Nuns Hospital||Recruiting|
|Edmonton, Alberta, Canada, T6L 5X8|
|Contact: Dan Stollery email@example.com|
|Nouvel Hôpital Civil||Recruiting|
|Strasbourg, France, F - 67091|
|Contact: Michel Hasselmann, MD firstname.lastname@example.org|
|Study Chair:||Daren K. Heyland, MD||Clinical Evaluation Research Unit, Kingston General Hospital|