Efficacy and Safety Study of a Low-carbohydrate Tube Feed in Critically Ill Patients Under Insulin Therapy

Effects of a Diabetes-specific Tube Feed on Glycemic Variability in Critically Ill Patients During Insulin Blood Glucose Management

The purpose of this study is to determine the efficacy and safety of a diabetes-specific tube feed in comparison to an isocaloric, isonitrogenous standard enteral formula in critically ill patients receiving insulin treatment for blood glucose management.

Study Overview

• Status: Terminated
• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Other: Diben 1.5 kcal HP; Other: Fresubin HP Energy Fibre (1.5 kcal)

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Universitätsklinikum Innsbruck

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with spontaneous aneurysmal subarachnoid hemorrhage (SAH) defined according to Hunt and Hess scale grade HH5
• Requiring mechanical ventilation in the ICU at the time of enrolment

• Enteral nutrition (EN) in the ICU at time of enrolment

  • If enrolment on day 3 of ICU stay, EN equal to or larger than 80% of total calories in case of supplementary parenteral nutrition (PN) with anticipated 100% EN as of day 4 to 8 of ICU stay
  • If enrolment on day 4 of ICU stay, 100% EN planned for at least 5 days from the time of enrolment
• Patients expected to stay in the ICU for at least 5 days following enrolment
• Age 18 - 75 years
• Glycemic control with intravenous insulin therapy to maintain a target glucose range between 110 mg/dL and 150 mg/dL (6.1 and 8.3 mmol/l)
• Informed consent according to local regulations for decisionally impaired subjects

Exclusion Criteria:

• Patients with septic shock at time of enrolment
• Participation in a clinical trial with any investigational product within 4 weeks before study
• Patients requiring a fibre free diet
• Total or supplementary parenteral nutrition (> 20% of total calories)
• Known or suspected intolerance or allergy to any component of the study product(s), e.g. galactosemia
• Gastrectomy
• Postpyloric nutrition
• Any clinical condition not allowing enteral nutrition (e.g. emesis, severe reflux, severe diarrhea)
• Known severe heart failure (NYHA class 4)
• Liver insufficiency / failure (male: ALAT > 150 U/l; female: ALAT > 120 U/l)
• Acute kidney failure (blood creatinine > 2.5 mg/dl)
• Body Mass Index < 18 or > 35 kg/m²
• Known or suspicion of drug abuse
• Pregnant or breast feeding women
• Patients with diabetes mellitus type I

Exclusion After Enrolment (Withdrawal of Subjects)

• Start of PN with more than 20% of total given energy amount/ day
• Insulin infusion stopped unexpectedly for > 12h for non-nutritional reasons
• Discharge from ICU
• Intolerable AEs
• Major protocol violation
• Withdrawal of informed consent
• Discontinuation of study treatment for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Diben 1.5 kcal HP; Diben 1.5 kcal HP, Food for Special Medical Purposes (diabetes-specific tube feed)	Other: Diben 1.5 kcal HP; Continuous (24h) application according to a standardized enteral feeding protocol via nasogastric tube or percutaneous endoscopic gastrostomy (PEG); pump-assisted application (Charriére (CH) > 8), duration according to patient's tolerance and requirements for a maximum of 5 days. Dosage: 21 - 24 kcal/kg body weight/day (corresponding to 14 to 16 ml/kg body weight/day).
Other: Fresubin HP Energy Fibre (1.5 kcal); Fresubin HP Energy Fibre (1.5 kcal), Food for Special Medical Purposes (standard tube feed)	Other: Fresubin HP Energy Fibre (1.5 kcal); Continuous (24h) application according to a standardized enteral feeding protocol via nasogastric tube or percutaneous endoscopic gastrostomy (PEG); pump-assisted application (Charriére (CH) > 8), duration according to patient's tolerance and requirements for a maximum of 5 days. Dosage: 21 - 24 kcal/kg body weight/day (corresponding to 14 to 16 ml/kg body weight/day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood glucose variability (within patient standard deviation of blood glucose values per day)	At Day 3 of intervention or the day prior to switch from intravenous to subcutaneous insulin administration, whichever comes first

Secondary Outcome Measures

Outcome Measure	Time Frame
Glucose variability	Days 2, 4 and 5 of intervention
Time to switch from intravenous to subcutaneous insulin administration	Days 1-6, daily
Insulin requirements in IU per day	Days 1 - 6, daily
Blood glucose levels	Days 1 - 6, daily
HbA1c	Days 1, 6, 28
Difference between target and given enteral nutrition (Compliance)	Days 2-6, daily
Cerebral and subcutaneous microdialysis: glucose	Days 1 - 6, daily
Cerebral and subcutaneous microdialysis: lactate/pyruvate ratio	Days 1 - 6, daily
Hospital mortality	Day 28
ICU mortality	Day 28
ICU length of stay	Day 28
Days of mechanical ventilation	Day 28
Non-gastrointestinal complications (AEs) to enteral nutrition and application	Days 2-6, daily
Gastro-intestinal intolerance (AEs, complications)	Days 2-6, daily

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Collaborators: OE Clinical Trial Center (KKS) Universität Innsbruck; International Medical Research - Partner GmbH; dsh statistical services GmbH
• Investigators: Principal Investigator: Ronny Beer, PD Dr. med., Medical University of Innsbruck, Department of Neurology, Neurocritical Care Unit

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: July 10, 2015
• First Submitted That Met QC Criteria: July 17, 2015
• First Posted (Estimate): July 21, 2015

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Blood glucose; Enteral nutrition; Tube feeding; Diet, carbohydrate-restricted; Aneurysmal Subarachnoid Hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: DBHP-001-CEN