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

NCT ID: NCT01206166

Last Updated: 2021-03-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2015-07-31

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).

Conditions

Critical Illness; Acute Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Enteral Nutrition + Parenteral Nutrition

Enteral nutrition with the addition of parenteral supplementation (Olimel 5.7%E/N9E).

Group Type: EXPERIMENTAL

Olimel (5.7%E / N9E)

Intervention Type: DRUG

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.

Enteral Nutrition Only

Enteral nutrition only - no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Olimel

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

Clinical Evaluation Research Unit at Kingston General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Daren K. Heyland

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daren K. Heyland, MD

Role: STUDY_CHAIR

Clinical Evaluation Research Unit, Kingston General Hospital

Locations

University of Colorado DHSC

Boulder, Colorado, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Mercy Hospital St. Louis

St Louis, Missouri, United States

Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, United States

The Ohio State Univsersity Medical Center

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Texas Health Science Center

Houston, Texas, United States

Erasme University Hospital

Brussels, , Belgium

Royal Alexandra Hospital

Edmonton, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Grey Nuns Hospital

Edmonton, Alberta, Canada

Nouvel Hôpital Civil

Strasbourg, , France

Countries

United States; Belgium; Canada; France

References

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.

Reference Type: BACKGROUND

PMID: 19572118 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15899538 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12853537 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17324665 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15185069 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28599676 (View on PubMed)

Other Identifiers

TOP-UP

Identifier Type: -

Identifier Source: org_study_id