Clinical trial NCT02378948: Nutritional Route In Esophageal Resection Trial II
Official title: Nutritional Route in Esophageal Resection Trial II (NUTRIENT II): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Neoplasms
Keywords: Esophagectomy
Nutrition
Oral feeding
Enteral feeding
Pulmonary complications
Anastomotic leakage
Quality of life
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
First posted: 2015-03-04
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Functional recovery
timeFrame: up to 4 weeks after surgery
Secondary outcomes:
measure: Pulmonary complications
timeFrame: up to 4 weeks after surgery
measure: Anastomotic leakage
timeFrame: up to 4 weeks after surgery
measure: Nutritional status (weight loss, intake)
timeFrame: postoperative day 2, 5 and 14
measure: Need for parenteral feeding/ placement of a nasojejunal feeding tube
timeFrame: up to 2 weeks after surgery
measure: Need for additional surgical, radiological or endoscopic interventions
timeFrame: up to 4 weeks after surgery
measure: 30-day surgical complications (classified according to Clavien-Dindo)
timeFrame: up to 4 weeks after surgery
measure: Other complications requiring treatment
timeFrame: up to 4 weeks after surgery
measure: Need for ICU admission and total length of ICU stay
timeFrame: up to 4 weeks after surgery
measure: Quality of life
timeFrame: 6 weeks after neoadjuvant treatment, 6 weeks, 3 months en 6 months postoperatively
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
state: Noord-Brabant
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
state: Overijssel
Study officials:
affiliation: Catharina Ziekenhuis Eindhoven
name: Misha DP Luyer, MD, PhD
role: STUDY_CHAIR
References:
citation: Berkelmans GH, Wilts BJ, Kouwenhoven EA, Kumagai K, Nilsson M, Weijs TJ, Nieuwenhuijzen GA, van Det MJ, Luyer MD. Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol for a multicentre open-label randomised controlled trial. BMJ Open. 2016 Aug 5;6(8):e011979. doi: 10.1136/bmjopen-2016-011979.