Impact of Supplemental Parenteral Nutrition in ICU Patients on Metabolic, Inflammatory and Immune Responses (SPN2)

Impact of Supplemental Parenteral Nutrition (SPN) on Energy Balance, and Infection Rate in Intensive Care Patients: Underlying Metabolic, Inflammatory and Immune Mechanisms.

Having previously demonstrated that supplemental parenteral nutrition to complete an insufficient enteral nutrition (EN) between D4 and D8 improves outcome after critical illness, by reducing infectious complications, the present trial aims at investigating the underlying carbohydrate and protein metabolism changes, as well as the immune and inflammatory modulations associated with this improvement.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Dietary supplement: Supplemental parenteral nutrition (SPN)

Detailed Description

Enrollment on day 3 of critically ill patients, without contraindication to EN, not achieving 60% of the ICU per protocol energy target.

Intervention: Randomization to either continued pure EN, or from day 4 to supplemental PN to complete EN at target validated by indirect calorimetry.

Measurements: Indirect calorimetry on Days 3, 4, 9 (twice). Primary endpoints = glucose and leucine metabolism On days 4 and 9-10: isotopic investigation of glucose metabolism, and immune and inflammatory responses// Day 9-10: isotopic investigation of protein (leucine) metabolism Secondary endpoints: Insulin requirements, area under the curve (AUC) of blood Glucose, infections after day 9, overall complications, length of mechanical ventilation, of ICU and hospital stay.

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

Contacts and Locations

Study Locations

• Switzerland
  • GE
    • Geneva, GE, Switzerland, 1211
      • Nutrition Unit, Geneva University Hospital
  • VD
    • Lausanne, VD, Switzerland, 1011
      • Service of Adult Intensive Care - CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 86 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• estimated duration of ICU stay > 5 days,
• estimated survival > 7 days,
• absence of contraindication to EN
• need for mechanical ventilation
• informed consent obtained from patients, close relative, or referring physician

Exclusion Criteria:

• refusal of the patient or of the next of kin
• age < 18 years
• non-functional digestive tract (short bowel, persistent ileus, proximal intestinal fistula high rate > 1.5 litres/day)
• already receiving PN before Day 3
• absence of a central venous catheter
• women who are pregnant (pregnancy test).
• Admission after cardiac arrest, or severe brain injury

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
No Intervention: Enteral nutrition only; Enteral nutrition to be progressed as soon as possible to energy target measured on day 3, and verified on day 4, using the usual facilitators (prokinetics)
Experimental: Supplemental parenteral nutrition; Addition of supplemental parenteral nutrition to complete the gap between energy delivered by enteral feeding and energy target measured on day 4. Aim: 100% of this target, and not exceeding it, no catch up for energy deficit accumulated before day 4.	Dietary supplement: Supplemental parenteral nutrition (SPN); The amount of energy delivered by SPN will depend on the indirect calorimetry measurement and actual enteral feed delivery. SPN will be reduced with progressing EN; Other Names: Standard industrial PN solutions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose and Leucine turnover	On D04:Infusion after priming of 6.6 2H2 glucose and NaH13CO3 On Day 09-10: Infusion after priming of NaH13CO3 and of L-[1-13C]-Leucine + repeat of the glucose sequence	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune and inflammatory impact of optimized target feeding	lymphocyte phenotypes: lymphocyte subpopulations (frequency), level of activation (CD69), memory markers, effectors, regulators; Cluster differentiation CD4, CD8, and natural killer (NK) phenotypes; Cell inflammatory response (WBA and PBMC) on D4 and D10±1: IL-2, TNF-α, interleukine-6 (IL-6), IL-1, TGF, IL-10, in culture for 24 to 48h ex vivo and post stimulation by memory mix and mitogens.; Serological inflammatory response (WBA and PBMC) on D4 and D10+1: TNF-α , IL-6, C-reactive protein (CRP): ex vivo with ELISA Nosocomial infections after day 8	10 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global outcome	Overall complications and organ failures, length of mechanical ventilation, length of ICU and hospital stay.	28 days / 90 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: University of Geneva, Switzerland
• Investigators: Principal Investigator: Mette M Berger, MD PhD, CHUV, Lausanne

Publications and helpful links

General Publications

• Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013 Feb 2;381(9864):385-93. doi: 10.1016/S0140-6736(12)61351-8. Epub 2012 Dec 3.
• Berger MM, Pantet O, Jacquelin-Ravel N, Charriere M, Schmidt S, Becce F, Audran R, Spertini F, Tappy L, Pichard C. Supplemental parenteral nutrition improves immunity with unchanged carbohydrate and protein metabolism in critically ill patients: The SPN2 randomized tracer study. Clin Nutr. 2019 Oct;38(5):2408-2416. doi: 10.1016/j.clnu.2018.10.023. Epub 2018 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: December 22, 2013
• First Posted (Estimate): December 30, 2013

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 16, 2018
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Energy requirements, Glucose turnover, Protein turnover
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: CE 371-13