Nutritional Route In Esophageal Resection Trial II (NUTRIENTII)

January 30, 2019 updated by: Misha D.P. Luyer, Catharina Ziekenhuis Eindhoven

Nutritional Route in Esophageal Resection Trial II (NUTRIENT II): a Randomized Controlled Trial

The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative functional recovery after an esophagectomy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Early oral feeding is safe and beneficial in most types of gastro-intestinal surgery and is a crucial part of fast track or enhanced recovery protocols. Following esophagectomy, fast track programs are increasingly being applied, resulting in a reduced length of stay, perioperative morbidity and hospital charges. In a previous feasibility study (Nutrient I trial) has been shown that direct oral intake following esophagectomy was feasible and did not result in an increase of major complications. It remains unclear what the best strategy is for nutrition in the early postoperative phase following esophagectomy. The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative recovery and pulmonary complications following esophagectomy.

Patients will be recruited at the outpatient clinic of the Catharina Hospital Eindhoven and the Hospital Group Twente.Patients will enroll in the early oral feeding group or the delayed oral feeding group. The early oral feeding group will receive liquid oral nutrition directly after surgery. Patients in the delayed oral feeding group will receive enteral tube feeding (via a jejunostomy) for 5-7 days (standard protocol in The Netherlands). After these 5-7 days a liquid oral diet is initiated.

Patient characteristics and clinical parameters are registered in an electronic database. All surgical complications are classified using the Clavien-Dindo classification15 (Appendix II). An independent investigator will check functional recovery daily. Data is provided by local investigator via an online checklist (electronic case report form / website). Quality of life and Symptoms are scored using the European organization for research and treatment of cancer questionnaire (QLQ-C30/EORTC-OG25)16 at baseline (5 weeks after neoadjuvant treatment), 6 weeks, 3 months and 6 months postoperatively. Cost-effectiveness is scored via EQ-5D-5L, iMTA Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ). Nutritional status will be measured using the actual caloric and protein intake versus the needed caloric and protein intake. Long-term outcome parameters such as local recurrence, overall and cancer-specific survival will be registered in a database until the end of the study.

The sample size calculation is based on functional recovery as primary outcome. Functional recovery is the time to surgical recovery according to the definition described previously. Patients in our historic cohort (1 week artificial nutrition) were at least considered functional recovered by a mean of 12 days post-surgery. Patients in the NUTRIENT I were at least functional recovered at day 10 postoperative (mean) following an esophagectomy. In this trial we consider a reduction of 2 days in functional recovery as clinically significant. Using a Power of 80%, an alpha of 5% and a standard deviation of 4 days, a total of 128 patients (64 patients in each group) is needed to show this difference. It is expected that the primary outcome will not be normally divided and therefore an extra 15% inclusion is necessary, requiring a total of 148 patients (74 patients in each group). Interim-analyses will be performed following 50 and 100 patients and will be checked by an independent physician.

All analyses will be done according to the intention-to-treat approach in which all randomized patients are included, regardless of adherence to study protocol. Occurrences of the primary and secondary endpoints are compared between the treatment groups. Results are presented as risk ratios with corresponding 95% confidence intervals. A two-tailed P < 0.05 is considered statistically significant. To compare the groups the data will be tested for normal distribution and an unpaired T-test will be performed when appropriate, otherwise the Mann-Whitney U or Chi-square tests.

Study Type

Interventional

Enrollment (Actual)

148

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord-Brabant
      • Eindhoven, Noord-Brabant, Netherlands, 5623EJ
        • Catharina Ziekenhuis Eindhoven
    • Overijssel
      • Almelo, Overijssel, Netherlands, 7609PP
        • Ziekenhuisgroep Twente

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients that undergo a (minimally invasive) esophagectomy with intrathoracic anastomosis.
  • written informed consent
  • age >18 years

Exclusion Criteria:

  • Inability for oral intake
  • Inability to place a surgical feeding jejunostomy
  • Mental retardation
  • Swallowing disorder
  • Achalasia
  • Malnutrition (defined as >15% weight loss just before start of the surgery)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early oral feeding
Liquid oral feeding directly after esophagectomy.
Dietary supplement: Liquid oral feeding
Liquid oral feeding (water, soup, porridge, nutritional supplements etc.)
No Intervention: Delayed oral feeding
Liquid oral feeding 5 days after esophagectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional recovery
Time Frame: up to 4 weeks after surgery
The primary outcome parameter is the day of functional recovery. Functional recovery is defined as postoperative patients who are free of IV fluid, have adequate pain control, restoration of mobility to an independent level, have sufficient caloric intake and no signs of active infection.
up to 4 weeks after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pulmonary complications
Time Frame: up to 4 weeks after surgery
(Pneumonia, Acute respiratory distress syndrome, respiratory insufficiency requiring treatment)
up to 4 weeks after surgery
Anastomotic leakage
Time Frame: up to 4 weeks after surgery
up to 4 weeks after surgery
Nutritional status (weight loss, intake)
Time Frame: postoperative day 2, 5 and 14
postoperative day 2, 5 and 14
Need for parenteral feeding/ placement of a nasojejunal feeding tube
Time Frame: up to 2 weeks after surgery
up to 2 weeks after surgery
Need for additional surgical, radiological or endoscopic interventions
Time Frame: up to 4 weeks after surgery
up to 4 weeks after surgery
30-day surgical complications (classified according to Clavien-Dindo)
Time Frame: up to 4 weeks after surgery
classified according to Clavien-Dindo
up to 4 weeks after surgery
Other complications requiring treatment
Time Frame: up to 4 weeks after surgery
i.e. urinary tract infection
up to 4 weeks after surgery
Need for ICU admission and total length of ICU stay
Time Frame: up to 4 weeks after surgery
up to 4 weeks after surgery
Quality of life
Time Frame: 6 weeks after neoadjuvant treatment, 6 weeks, 3 months en 6 months postoperatively
6 weeks after neoadjuvant treatment, 6 weeks, 3 months en 6 months postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Catharina Ziekenhuis Eindhoven

Investigators

  • Study Chair: Misha DP Luyer, MD, PhD, Catharina Ziekenhuis Eindhoven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

June 12, 2018

Study Completion (Actual)

November 1, 2018

Study Registration Dates

First Submitted

February 23, 2015

First Submitted That Met QC Criteria

February 26, 2015

First Posted (Estimate)

March 4, 2015

Study Record Updates

Last Update Posted (Actual)

January 31, 2019

Last Update Submitted That Met QC Criteria

January 30, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL52591.060.15

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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