Enteral vs. Oral Nutrition After Pancreatoduodenectomy (NUTRIWHI)

Early Enteral vs. Oral Nutrition After Whipple Procedure: a Multicentric Randomized Controlled Trial

Patients suffering from pancreas cancer as well as patients with chronic pancreatitis or requiring pancreas surgery often are in a compromised nutritional status. Nutritional support should therefore be started early during the postoperative course to prevent further malnutrition, as it is an important risk factor to develop complications. Recently, several studies have shown that early enteral nutrition (EEN) could shorten length of stay, reduce postoperative infections and mortality, and decrease costs when compared with total parenteral nutrition (TPN) in gastrointestinal cancer surgery. After pancreatoduodenectomy (PD), EEN has been shown to reduce early and late complications, infections, and readmission rates. It is nevertheless currently not clear if EEN improves the short-term outcomes after PD compared to oral nutrition.

The primary objective of the study is to assess the impact of EEN on postoperative morbidity after PD, according to the Comprehensive Complication Index. Secondary objectives are to assess the impact of EEN on major postoperative complications, according to Clavien classification, specific complications, length of stay, readmission rates, quality of life, metabolic stress and nutritional response after PD.

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Malnutrition; Pancreaticoduodenectomy
• Intervention / Treatment: Dietary supplement: Early enteral nutrition

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Hôpital Cochin-Port Royal, AP-HP
• Switzerland
  • Ticino
    • Lugano, Ticino, Switzerland
      • Regional Hospital of Lugano
  • Vaud
    • Lausanne, Vaud, Switzerland
      • Lausanne University Hospital (CHUV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient scheduled for elective open pancreatoduodenectomy.
• Patient ≥18 years old.
• Patient at nutritional risk, i.e., with Nutrition Risk Screening (NRS) ≥3.
• Signed informed consent.

Exclusion Criteria:

• Patient not able to give informed consent as documented by signature of consent form (e.g., vulnerable patients).
• Enteral feeding already initiated preoperatively.
• Language barrier.
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders (i.e., eating disorders and bipolar disorders), or dementia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early enteral nutrition; Intervention group: enteral nutrition from the first postoperative night until 50% of caloric requirements are covered by oral nutrition. Enteral nutrition will start at a flow of 250 ml/12h. If tolerated, enteral nutrition will be increased to 500 ml/12h on postoperative day 1, 750 ml/12h on postoperative day 2, and 1000 ml/12h on postoperative day 3. A hypercaloric enteral nutrition will be used (Isosource Energy Fibre or similar).	Dietary supplement: Early enteral nutrition; Enteral nutrition via nasojejunal tube
No Intervention: Oral nutrition; Control group: patients will receive standardized oral nutrition. The night after the operation, patients will be allowed to have free drinks. On postoperative day 1, they will receive bouillons, creams, yogurts, and drinks >2 l. On postoperative day 2, they will receive a light diet. On postoperative day 3, they will receive half portion of normal diet and on postoperative day 4 normal diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive Complication Index	Index measuring all complications for a patient	Postoperative day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe postoperative complications	Dindo-Clavien >II	Postoperative day 90
Specific complications after pancreatoduodenectomy	SSI, DGE, POPF, PPH, biliary fistula, gastrojejunal anastomosis fistula, pancreatitis	Postoperative day 90
Length of stay	From operation day to hospital discharge	Up to 90 days
Readmission	Hospital readmission due to surgical complications	Postoperative day 90
Patients' quality of life	EORTC questionnaires	Preoperatively and at 30 and 90 days after the operation
Metabolic response to enteral nutrition	Laboratory results	Preoperatively and twice weekly during the first postoperative week
Body composition	Bioelectrical impedance analysis	Preoperatively and on the day when patients leave the hospital after the operation
Muscular measure	Handgrip strength measure	Preoperatively and on the day when patients leave the hospital after the operation
Resting energy expenditure	Indirect calorimetry	On postoperative day 5

Collaborators and Investigators

• Sponsor: University of Lausanne Hospitals
• Investigators: Study Chair: Nicolas Demartines, MD, University of Lausanne Hospitals; Principal Investigator: Gaëtan-Romain Joliat, MD, University of Lausanne Hospitals; Study Director: Markus Schäfer, MD, University of Lausanne Hospitals

Publications and helpful links

General Publications

• Joliat GR, Martin D, Labgaa I, Melloul E, Uldry E, Halkic N, Fotsing G, Cristaudi A, Majno-Hurst P, Vrochides D, Demartines N, Schafer M. Early enteral vs. oral nutrition after Whipple procedure: Study protocol for a multicentric randomized controlled trial (NUTRIWHI trial). Front Oncol. 2022 Jun 28;12:855784. doi: 10.3389/fonc.2022.855784. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2021
• Primary Completion (Actual): January 13, 2025
• Study Completion (Actual): January 13, 2025

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Morbidity; Pancreatoduodenectomy; Enteral nutrition; Pancreas surgery; Oral nutrition; Whipple operation
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Malnutrition; Postoperative Complications
• Other Study ID Numbers: 2021-00724

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No