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Trial registered on ANZCTR


Registration number
ACTRN12611000178943
Ethics application status
Approved
Date submitted
31/08/2010
Date registered
15/02/2011
Date last updated
15/02/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of pre- and peri operative immunonutrition to standard formula in patients undergoing surgical resection of oesophageal cancer
Scientific title
The effect of pre- and perioperative immunonitrition versus standard formula on post-operative complications, mortality, length of stay, quality of life and nutritional outcomes in patients undergoing surgical resection of oesophageal cancer
Secondary ID [1] 252603 0
Nil
Universal Trial Number (UTN)
U1111-1116-7903
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients undergoing oesophagectomy for cancer resection 258101 0
Condition category
Condition code
Surgery 258276 258276 0 0
Other surgery
Cancer 258277 258277 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be a multicentre, prospective, double blind, RCT with a 2 x 2 factorial design

Participants (N= 232) will be randomised to receive:

Arm 1: Pre-operative immunonutrition and post-operative immunonutrition (n=58)
Arm 2: Pre-operative immunonutrition and post-operative control nutrition (n=58)
Arm 3: Pre-operative control nutrition and post-operative immunonutrition (n=58)
Arm 4: Pre-operative control nutrition and post-operative control nutrition (n=58)

Pre-operative supplement- Active

Participants are required to consume orally, in addition to their normal diet, 3 x 74g sachets of pre-operative supplement to be dissolved in water up to 900ml for seven days prior to surgery (21 sachets total/ participant). Patients who have total dysphagia will be fed enterally (either nasoenteric or jejunostomy feeding tube).

The oral immunonutrition supplement contains 909kCal, 50.4g total protein (includes 11.4g free L-arginine), 3.0g omega-3 fatty acids EPA, DHA and alpha linolenic acid (LNA) and 1.2g RNA per 900ml.

Post-operative supplement- Active

Patients will be fed the post-operative formula supplement for 7 days consecutive days after oesophagectomy via their jejunostomy which will be inserted during the oesophagectomy procedure. Feeding will commence on day +1 following surgery at a rate of 40ml/hr (for 24 hours) unless otherwise indicated by the treating surgeon or delegate. Feeds will be upgraded daily if tolerated in 20ml increments to the maximum rate required to meet 100% of their estimated postoperative energy and protein requirements or at the treating surgeon/ delegate’s discretion. The total volume of fluid should not exceed 90mls/hr without the treating surgeon/ delegate’s approval.

The post-operative immunonutrition supplement formula contains 1010kCal, 56g total protein (includes 13g arginine), 3.3g omega-3 fatty acids EPA, DHA & LNA and 1.3g RNA per 1000ml.
Intervention code [1] 257124 0
Treatment: Other
Intervention code [2] 257163 0
Prevention
Comparator / control treatment
Pre-operative supplement- Control

Participants randomised to the pre-op control group are required to consume orally, in addition to their normal diet, 3 x 74g sachets of supplement to be dissolved in water up to 900ml for seven days prior to surgery (21 sachets total/ participant). Patients who have total dysphagia will be fed enterally (either nasoenteric or jejunostomy feeding tube). The oral control supplement contains 909kCal, 39g total protein (without free L-arginine), nil omega 3 fatty acids or RNA per 900ml.


Post-operative supplement- Control
Patients randomised to the control group post-op will be fed as per the active group. Nursing staff, Dietetic Assistant/Aides or Dietitians will be blinded to the type of supplement allocated to the patient. The feeds will be labelled “trial formula”. There is no difference in administration between the active and control groups. The post-operative control supplement formula contains 1020kCal, 70g total protein and does not contain added arginine, omega 3 fatty acids or RNA.
Control group
Active

Outcomes
Primary outcome [1] 259119 0
Incidence of infective complications including: intra-abdominal abcess, wound infection, respiratory infection, sepsis, urinary tract infection (UTI).

These outcomes will be assessed using a standardised predetermined proforma as per the definitions below by a blinded member of the surgical team (either the consultant or senior registrar).

Intra-abdominal Abscess= deep collection of pus

Wound Infection= any redness or tenderness of the surgical wound with discharge of pus

Pulmonary Infection= abnormal chest x-ray with fever (Temperature > 38 degrees celsius) and white blood cell (WBC) count >12 x103/ul and positive sputum or bronchoalveloar lavage

UTI= >107 microorganisms per ml

Septicemia = Positive blood culture or Systemic Inflammatory Response Syndrome (SIRS):Pyrexia > 38 degrees celsius, WBC >12 000 or < 4000/ mm3, achycardia >100/ min or Tachypnoea > 18/ min
Timepoint [1] 259119 0
Day 14 post surgery
Day 42 post-surgery
Primary outcome [2] 259120 0
Incidence of non-infective complications: acute lung injury, chylothorax and anastomotic leak.

These outcomes will be assessed using a standardised predetermined proforma as per the definitions below by a blinded member of the surgical team (either the consultant or senior registrar).

Acute Respiratory Distress Syndrome (ARDS)/ Acute Lung Injury = ARDS diagnosis is made if ALL of the following criteria are met:
1. Acute onset
2. Pulmonary Artery wedge pressure <18.1 mmHg (when available)
3. Bilateral infiltrates on chest radiography
4. PaO2: FiO2 <200
5. Predisposing condition (i.e. Oesophagectomy)

Chylothorax= Presence of milky white fluid in the drain or chest containing white blood cells, red blood cells, protein, triglycerides, cholesterol, cholesterol esters, pancreatic lipase and amylase

Anastomotic leak= any dehiscence with clinical or radiologic evidence
Timepoint [2] 259120 0
Day 14 post-surgery
Day 42 post-surgery
Secondary outcome [1] 265433 0
Incidence of Mortality.

Date and cause of death will be recorded by either the site Dietitian or a member of the treating surgical team using the patient medical records.
Timepoint [1] 265433 0
Day 9 post-surgery
Day 42 post surgery
Secondary outcome [2] 265434 0
Length of stay (LOS) in Intensive Care Unit (ICU) and hospital admission.

LOS will be determined from hospital medical records and recorded by a blinded member of the surgical team.
Timepoint [2] 265434 0
Between time of surgery until date of discharge from hospital.

In the event a patient cannot be discharged due to other reasons (e.g. social), the date when the patient was deemed fit to be discharged will be recorded.
Secondary outcome [3] 265435 0
Nutritional status assessed by the Patient-Generated Subjective Global Assessment (PG-SGA).

The PG-SGA is a validated tool for assessing the nutritional status of cancer patients. This tool provides a global rating of either A (well nourished), B (suspected or moderately malnourished) or C (severely malnourished). This global rating is based upon weight change, dietary intake, gastro-intestinal symptoms, a physical examination and the patient's functional capacity. A total PG-SGA score is also calculated. A higher score reflects a higher risk of malnutrition and an increased need for nutrition intervention and symptom management.

The site Dietitians conducting this assessment will undergo training and testing for inter-rater reliability on nutritional status measures prior to commencing data collection.
Timepoint [3] 265435 0
1 week pre-surgery
Day 1 pre-surgery
Day 9 post-surgery
Day 42 post-surgery
Secondary outcome [4] 265436 0
Quality of Life (QOL).

QOL will be assessed using three tools;

1. the general oncology QOL tool: the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 (version 3.0)

2. the oesophageal cancer-specific QOL tool; the EORTC QLQ-OESI8 (phase III module)

3. the EuroQoL (EQ-5D) which takes less than a few minutes to complete and will be used in the health economic analysis
Timepoint [4] 265436 0
1 week pre-surgery
Day 42 post-surgery
Secondary outcome [5] 265437 0
Albumin and C-reactive protein (CRP).

Blood Tests will be performed to assess Albumin and CRP plasma levels.
Timepoint [5] 265437 0
1 week pre-surgery
Day 1 pre-surgery
Day 9 post-surgery
Day 42 post-surgery

Eligibility
Key inclusion criteria
Histologically proven neoplasm of the oesophagus or gastro oesophageal junction

Patients scheduled for oesophagectomy or oesophago-gastrectomy and insertion of a feeding jejunostomy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients requiring parenteral nutrition

Pregnancy

Cognitive or other limitations preventing patient from being able to provide informed consent

Taking fish oil or fish oil capsules, flaxseed oil or flaxseed capsules, cod liver oil or cod liver capsules or consuming products enriched with immunonutrients eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arginine (e.g. ProSure or Resource Support or Forticare) within 2 weeks of the proposed surgery or not willing to cease these products at least 2 weeks prior to the proposed surgery.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be assessed to ensure that they meet the inclusion and exclusion criteria. All patients who meet the criteria will be invited to participate in the study and be given a participant information sheet. This process may occur at any stage up to within seven days of surgery.

The investigator must keep a log of all patients screened (both eligible and not eligible) and a confidential record of all eligible patients recruited into the study. Patients who undergo any study related procedures (and thus assign a patient screening number) but fail to receive study treatment for any reasons will be included in the analysis of the study. A screening and enrolment log, which documents the screening number, patient initials and reason(s) for screen failure is to be maintained by the investigator. A copy of the log must be retained in the investigator’s study file.

A consenting patient will be allocated the treatment by a Randomiser independent of the study, who will provide the staff responsible for the dispensing the treatment (either Pharmacy or Food Service Staff independent of the study) the treatment allocation in a sealed opaque envelope. The dispensed treatment will be decoded and labelled ‘trial product’ so that neither the patient, nor the ward nursing staff administering the ‘trial product’ are aware of the treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patient numbers will be assigned sequentially to patients as soon as they sign the informed consent form.

At each site, patients will be randomly assigned in variable blocks using a computer generated randomisation sequence. The randomisation sequence will be kept separately from the study investigators.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/08/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
232
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment postcode(s) [1] 3207 0
5000
Recruitment postcode(s) [2] 3208 0
5042
Recruitment postcode(s) [3] 3209 0
4101
Recruitment postcode(s) [4] 3210 0
4102
Recruitment postcode(s) [5] 3211 0
5005

Funding & Sponsors
Funding source category [1] 257564 0
Government body
Name [1] 257564 0
National Health and Medical Research Council
Country [1] 257564 0
Australia
Primary sponsor type
Individual
Name
Professor Glyn Jamieson
Address
Discipline of Surgery
University of Adelaide
Level 5 Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide, SA ,5005
Country
Australia
Secondary sponsor category [1] 257636 0
Individual
Name [1] 257636 0
Ms Louise Mudge
Address [1] 257636 0
Senior Dietitian, Trial Coordinator
Discipline of Surgery,
University of Adelaide
Level 5 Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5005
Country [1] 257636 0
Australia
Other collaborator category [1] 251469 0
Individual
Name [1] 251469 0
Associate Professor Bernard Mark Smithers
Address [1] 251469 0
Mater Medical Centre ,
GIAST Clinic, Suites 30-32,
293 Vulture Street,
South Brisbane, QLD 4101
Country [1] 251469 0
Australia
Other collaborator category [2] 251470 0
Individual
Name [2] 251470 0
Professor David Watson
Address [2] 251470 0
Flinders Medical Centre,
Flinders University, Department of Surgery,
3 Flinders Drive,
Bedford Park, SA, 5042
Country [2] 251470 0
Australia
Other collaborator category [3] 251816 0
Individual
Name [3] 251816 0
Dr Liz Isenring
Address [3] 251816 0
The University of Queensland,
School of Human Movement Studies,
level 4 Connell Building,
Brisbane, Qld 4072
Country [3] 251816 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259586 0
The Royal Adelaide Hospital Ethics Committee
Ethics committee address [1] 259586 0
Ethics committee country [1] 259586 0
Australia
Date submitted for ethics approval [1] 259586 0
31/05/2007
Approval date [1] 259586 0
11/06/2007
Ethics approval number [1] 259586 0
070526
Ethics committee name [2] 259587 0
Mater Health Services Human Research Ethics Committee
Ethics committee address [2] 259587 0
Ethics committee country [2] 259587 0
Australia
Date submitted for ethics approval [2] 259587 0
15/06/2010
Approval date [2] 259587 0
09/07/2010
Ethics approval number [2] 259587 0
1519P
Ethics committee name [3] 259588 0
Metro South Human research Ethics Committee
Ethics committee address [3] 259588 0
Ethics committee country [3] 259588 0
Australia
Date submitted for ethics approval [3] 259588 0
15/06/2010
Approval date [3] 259588 0
19/08/2010
Ethics approval number [3] 259588 0
10/QPAH/73
Ethics committee name [4] 259589 0
Flinders Medical Centre Human Research Ethics Committee
Ethics committee address [4] 259589 0
Ethics committee country [4] 259589 0
Australia
Date submitted for ethics approval [4] 259589 0
27/08/2010
Approval date [4] 259589 0
Ethics approval number [4] 259589 0
Ethics committee name [5] 259590 0
St Andrew's Hospital Human Research Ethics Committee
Ethics committee address [5] 259590 0
Ethics committee country [5] 259590 0
Australia
Date submitted for ethics approval [5] 259590 0
09/08/2010
Approval date [5] 259590 0
Ethics approval number [5] 259590 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31590 0
Address 31590 0
Country 31590 0
Phone 31590 0
Fax 31590 0
Email 31590 0
Contact person for public queries
Name 14837 0
Melissa Colombo & Louise Mudge
Address 14837 0
Royal Adelaide Hospital
Discipline of Surgery, University of Adelaide
Level 5 Eleanor Harrald Building,
North Terrace, Adelaide, SA 5005
Country 14837 0
Australia
Phone 14837 0
+61 8 82222854
Fax 14837 0
+61 8 82225896
Email 14837 0
melissa.colombo@adelaide.edu.au
Contact person for scientific queries
Name 5765 0
Professor Glyn G Jamieson
Address 5765 0
Royal Adelaide Hospital
Discipline of Surgery, University of Adelaide
Level 5 Eleanor Harrald Building,
North Terrace, Adelaide, SA 5005
Country 5765 0
Australia
Phone 5765 0
+61 8 82225516
Fax 5765 0
+61 8 82225896
Email 5765 0
glyn.jamieson@adelaide.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseMulticentre factorial randomized clinical trial of perioperative immunonutrition versus standard nutrition for patients undergoing surgical resection of oesophageal cancer.2018https://dx.doi.org/10.1002/bjs.10923
Dimensions AIResponsiveness and convergent validity of QLU-C10D and EQ-5D-3L in assessing short-term quality of life following esophagectomy2021https://doi.org/10.1186/s12955-021-01867-w
N.B. These documents automatically identified may not have been verified by the study sponsor.