Randomised oesophagectomy: minimally invasive or open - comparing different approaches to surgery

ISRCTN	ISRCTN10386621
DOI	https://doi.org/10.1186/ISRCTN10386621
IRAS number	184167
Secondary identifying numbers	30470

Submission date: 18/05/2016
Registration date: 31/05/2016
Last edited: 26/03/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-different-types-of-surgery-for-cancer-of-the-food-pipe-romio-study

Study website

Contact information

Prof Chris Metcalfe
Public, Scientific, Principal Investigator

University of Bristol
1-5 Whiteladies Road
Bristol
BS8 1NU
United Kingdom

ORCID ID	0000-0001-8318-8907
Phone	+44 117 455 4502
Email	chris.metcalfe@bristol.ac.uk

Study information

Study design	Pragmatic multicentre interventional randomized controlled trial (RCT) with qualitative component
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	ROMIO: Randomised Oesophagectomy - Minimally Invasive or Open
Study acronym	ROMIO
Study objectives	Laparoscopically-assisted oesophagectomy (LAO) is superior compared to standard open oesophagectomy (OO) with respect to recovery from surgery.
Ethics approval(s)	South West Frenchay Research Ethics Committee, 11/05/2016, ref: 16/SW/0098
Health condition(s) or problem(s) studied	Oesophageal cancer
Intervention	Patients will be randomised to either open oesophagectomy (OO) or "laparoscopically assisted" oesophagectomy (LAO) using an internet-based randomisation system. Both treatments are provided as standard on the NHS. OO and LAO both consist of identical steps, except that the abdominal phase of the operation in the LAO group will be done through several smaller cuts to the tummy and performed laparoscopically. The duration of treatment is the duration of surgery. Patients will be followed up using questionnaires for 24-36 months after randomisation into the study (36 month follow-up will only be completed if it falls within the planned length of the study). Added 18/08/2017: In Bristol and Southampton patients may be randomised to a third group - Totally Minimally Invasive Oesophagectomy (TMIO). The ROMIO study includes a nested IDEAL Phase 2b study looking at TMIO.
Intervention type	Procedure/Surgery
Primary outcome measure	Assessment of physical function, using the mean of a subscale of the EORTC QLQ-C30, carried out at 3 and 6 weeks post-surgery and 3 months after randomisation
Secondary outcome measures	1. All cause short and long term complications 2. Impact of the 30-day complications will be categorised using the Clavien-Dindo System 3. Lung function is measured using spirometry measures of forced expiratory volume 1 and forced vital capacity 4. Success of blinding during the first 6 days post-surgery is determined using the Bang Blinding Index procedure 5. Generic and disease specific health-related quality of life measures are determined using EORTC QLQ-C30 and QLQ-OES18, multidimensional fatigue inventory (MFI-20), EuroQOLEQ-5D-5L 6. Quality assurance of surgery with histopathological and surgical measures 6.1. Histopathological measures (with the pathologist assessing these blind to treatment allocation) 6.1.1. Length of the oesophagus 6.1.2. Total count of malignant ‘positive’ nodes 6.1.3. Total count of all nodes 6.1.4. Rates of positive circumferential resection margins 6.1.5. Rates of positive proximal and distal resection margins 6.1.6. pT stage (proportions of patients with each pT stage) 6.2. Surgical measures assessed by a surgeon blind to patient allocation 6.2.1. Quality of abdominal lymphadenectomy 6.2.2. Quality of mediastinal lymphadenectomy 7. Overall and disease-free survival to 2 years 8. Length of hospital stay, defined as length of primary hospital stage plus readmission within 30 days (and length of primary hospital stay plus length of hospital stay if discharged to community hospital). 9. Further measures of resource use including: staff time and resources used in theatre in the interventions; subsequent inpatient stays, outpatient visits, general practitioner visits and other community based resource use
Overall study start date	01/12/2015
Completion date	31/08/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 446; UK Sample Size: 446
Total final enrolment	363
Key inclusion criteria	1. 18 years of age or above 2. Referred for primary oesophagectomy by the multi-disciplinary team (MDT) or oesophagectomy following re-staging after neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (N.B, in this any type of neoadjuvant treatment may be used) 3. Confirmed MDT evidence of at least adenocarcinoma or at least squamous cell cancer of the oesophagus or oesophago-gastric junction 4. Fit for pre-operative anaesthesia and surgery, assessed by the MDT 5. Able to provide written informed consent 6. Measurement (endoscopic or otherwise) that the tumour starts more than 5 cm below crico-pharyngeus 7. Measurement (endoscopic or otherwise) that the tumour involves less than 4 cm of the gastric wall 8. The final pre-treatment tumour stage is between T1N0M0 and T4aN1M0, i.e. including all stages (T1N0M0, T1N1M0, T1N2M0, T2N0M0, T2N1M0, T2N2M0, T3N0M0, T3N1M0, T3N2M0, T4aN0M0 and T4aN1M0) in which T4a is a resectable tumour invading pleura, pericardium, or diaphragm
Key exclusion criteria	Current exclusion criteria as of 18/08/2017: 1. Patients with high grade dysplasia (squamous cell or adenocarcinoma) 2. Patients with T4b, or any stage with M1 3. Type 3 tumours of the oesophago-gastric junction that are scheduled for total gastrectomy 4. Patients with squamous cell cancer of the oesophagus who the MDT recommends or who individually elect to undergo definitive chemoradiotherapy 5. Evidence of previous complex thoracotomies or laparotomies that preclude a minimal access approach 6. Evidence of previous/concomitant malignancy that would interfere with this treatment protocol 7. Pregnancy 8. Patients participating in other trials that would interfere with the implementation of this protocol at a particular site Previous exclusion criteria: 1. Patients with high grade dysplasia (squamous cell or adenocarcinoma) 2. Stage 4 disease 3. Type 3 tumours of the oesophago-gastric junction that are scheduled for total gastrectomy 4. Patients with squamous cell cancer of the oesophagus who the MDT recommends or who individually elect to undergo definitive chemoradiotherapy 5. Evidence of previous complex thoracotomies or laparotomies that preclude a minimal access approach 6. Evidence of previous/concomitant malignancy that would interfere with this treatment protocol 7. Pregnancy 8. Patients participating in other trials that would interfere with the implementation of this protocol at a particular site
Date of first enrolment	01/06/2016
Date of final enrolment	21/08/2019

Locations

Countries of recruitment

England
Scotland
United Kingdom

Study participating centres

Bristol Royal Infirmary

Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Derriford Hospital

Plymouth Hospitals NHS Foundation Trust
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Southampton General Hospital

University Hospital Southampton NHS Foundation Trust
Tremona Road
Southampton
SO16 6YD
United Kingdom

Royal Infirmary of Edinburgh

NHS Lothian
GI Surgery
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom

Leicester Royal Infirmary

University Hospitals of Leicester NHS Trust#
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Royal Preston Hospital

Lancashire Teaching Hospitals NHS Foundation Trust
Chief Executive's Office
Sharoe Green Lane
Preston
PR2 9HT
United Kingdom

Salford Royal

Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Nottingham City Hospital

Upper GI Surgery
City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Royal United Hospitals Bath

Royal United Hospitals Bath NHS Foundation Trust
Combe Park
Bath
BA1 3NG
United Kingdom

Sponsor information

University Hospitals Bristol NHS Foundation Trust
Hospital/treatment centre

Research & Innovation
Level 3 Education & Research Centre
Upper Maudlin Street
Bristol
BS2 8AE
England
United Kingdom

"ROR"	https://ror.org/04nm1cv11

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	01/04/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned dissemination of the main trial results (clinical and cost-effectiveness) to surgeons and other clinicians through publication in a high profile journal which allows open access (to be published after the study has ended). This will be preceded by publication of the design of the definitive trial, allowing a fuller description of the methods, so enabling better understanding of the results. The study and results will also be disseminated at conferences attended by surgeons, such as the annual Association of Upper Gastro Intestinal Surgeons (AUGIS) meeting, and the NCRI Upper GI Clinical Studies Group Annual Trials Meeting.
IPD sharing plan	The datasets generated during and/or analysed during the current study will not be made available for sharing until after publication of the main results of the research. Thereafter, anonymised individual patient data will be made available for secondary research, conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the MRC Policy on Data Preservation and Sharing regarding scientific quality, ethical requirements and value for money. A minimum requirement with respect to scientific quality will be a publicly available pre-specified protocol describing the purpose, methods and analysis of the secondary research, e.g. a protocol for a Cochrane systematic review. The second file containing patient identifiers would be made available for record linkage or a similar purpose, subject to confirmation that the secondary research protocol has been approved by a UK REC or other similar, approved ethics review body.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	quality assurance protocol	01/03/2019	30/03/2020	Yes	No
Protocol article	protocol	19/11/2019	27/10/2020	Yes	No
HRA research summary			28/06/2023	No	No
Statistical Analysis Plan	version 1	12/09/2019	02/01/2024	No	No
Statistical Analysis Plan	version 1	12/09/2019	02/01/2024	No	No
Plain English results			25/03/2024	No	Yes
Results article		02/03/2024	26/03/2024	Yes	No

Additional files

ISRCTN10386621_SAP_v1_01Sep2019.pdf

Editorial Notes

26/03/2024: Publication reference added.
25/03/2024: A link to plain English results on CRUK was added.
02/01/2024: The following changes have been made:
1. A statistical analysis plan (SAP) has been uploaded and linked.
2. The previous public contact has been removed and a new principal investigator/scientific contact/public contact has been added.
3. The IRAS number has been added.
4. The intention to publish date has been changed from 01/04/2023 to 01/04/2024.
03/12/2021: The following changes have been made:
1. The study design has been changed from "Both; Both; Design type: Treatment, Surgery, Qualitative" to "Pragmatic multicentre interventional randomised controlled trial (RCT) with qualitative component".
2. The overall trial end date has been changed from 01/04/2022 to 31/08/2021.
3. The trial website has been added.
4. Royal United Hospitals Bath has been added to the trial participating centres.
27/10/2020: Publication reference added.
30/03/2020: Publication reference added.
14/01/2020: The public contact has been changed.
18/10/2019: The following changes have been made:
1. The final enrolment number has been added.
2. The recruitment end date was changed from 30/09/2019 to 21/08/2019.
3. The overall trial end date has been changed from 30/05/2021 to 01/04/2022.
4. The intention to publish date has been changed from 30/05/2022 to 01/04/2023.
24/04/2019: The trial contact details have been updated.
02/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Upper GI; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs" to "Oesophageal cancer" following a request from the NIHR.
06/03/2019: The recruitment end date has been changed from 28/02/2019 to 30/09/2019.
20/12/2018: The recruitment end date has been changed from 01/12/2018 to 28/02/2019.
18/08/2017: Exclusion criteria and interventions updated, Nottingham City Hospital added as a trial participating centre, IPD sharing statement added.
19/12/2016: Cancer Help UK lay summary link added.