Clinical trial NCT01206166: Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients (TOP-UP)
Official title: A Randomized Trial of Supplemental Parenteral Nutrition in Under and Over Weight Critically Ill Patients: The TOP UP Trial (Pilot)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Critical Illness
Acute Respiratory Failure
Keywords: Randomized trial
Parental nutrition
Enteral nutrition
Intensive care unit
BMI < 25 or ≥ 35
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2010-09-21
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility 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

Primary outcomes:
measure: Calorie & Protein Intake 7 Days Post Randomization
timeFrame: 7 days post randomization
measure: Calorie & Protein Intake in First 27 Days
timeFrame: first 27 days
Secondary outcomes:
measure: 6 Month Mortality
timeFrame: 6 months
measure: ICU Mortality
timeFrame: 6 months
measure: Hospital Mortality
timeFrame: 6 months
measure: Duration of ICU Stay
timeFrame: 6 months
measure: Duration of Hospital Stay
timeFrame: 6 months
measure: Duration of Mechanical Ventilation
timeFrame: 6 months
measure: Development of ICU-acquired Infections
timeFrame: ICU discharge
measure: SF36-Physical Functioning Domain
timeFrame: 3 months
measure: SF-36 Physical Functioning Domain
timeFrame: 6 months
measure: Functional Status at Hospital Discharge
timeFrame: hospital discharge
measure: SF36 Role Physical Domain
timeFrame: 3 months
measure: SF36 Pain Index Domain
timeFrame: 3 months
measure: SF36 General Health Perceptions Domain
timeFrame: 3 months
measure: SF36 Vitality Domain
timeFrame: 3 months
measure: SF36 Social Functioning Domain
timeFrame: 3 months
measure: SF36 Role-emotional Domain
timeFrame: 3 months
measure: SF36 Mental Health Index Domain
timeFrame: 3 months
measure: SF36 Standardized Physical Component Scale
timeFrame: 3 months
measure: SF36 Standardized Mental Component Scale
timeFrame: 3 months
measure: SF-36 Role-physical Domain
timeFrame: 6 months
measure: SF-36 Pain Index Domain
timeFrame: 6 months
measure: SF-36 General Health Perceptions Domain
timeFrame: 6 months
measure: SF-36 Vitality Domain
timeFrame: 6 months
measure: SF-36 Social Functioning Domain
timeFrame: 6 months
measure: SF-36 Role-emotional Domain
timeFrame: 6 months
measure: SF-36 Mental Health Index Domain
timeFrame: 6 months
measure: SF-36 Standardized Physical Component Scale
timeFrame: 6 months
measure: SF-36 Standardized Mental Component Scale
timeFrame: 6 months
Other outcomes:
Locations:
city: Boulder
country: United States
facility: University of Colorado DHSC
state: Colorado
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Lerner College of Medicine
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univsersity Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Hospital
state: Alberta
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
Study officials:
affiliation: Clinical Evaluation Research Unit, Kingston General Hospital
name: Daren K. Heyland, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.