Video-assisted thoracoscopic lobectomy (VATS) versus conventional Open Lobectomy for lung cancer

ISRCTN	ISRCTN13472721
DOI	https://doi.org/10.1186/ISRCTN13472721
ClinicalTrials.gov number	NCT03521375
Secondary identifying numbers	HTA 13/04/03

Submission date: 27/11/2014
Registration date: 28/11/2014
Last edited: 26/01/2024

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-keyhole-surgery-with-open-surgery-for-people-with-lung-cancer-violet

Study website

Contact information

Ms Surinder Kaur
Public

Bristol Trials Centre (CTEU)
Bristol Medical School, University of Bristol
Level 7
Queen's Building
Bristol Royal Infirmary
Marlborough Street
Bristol
BS2 8HW
United Kingdom

Phone	+44 (0)117 342 2987
Email	violet-study@bristol.ac.uk

Mr Eric Lim
Scientific

Academic Division of Thoracic Surgery
The Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom

Study information

Study design	Pragmatic multi-centre parallel-group randomised controlled trial with an internal pilot phase (phase 1)
Primary study design	Interventional
Secondary study design	Randomised parallel trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	VIdeo-assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer: a multi-centre randomised controlled trial with an internal pilot
Study acronym	VIOLET
Study hypothesis	VIOLET is an interventional study to evaluate the effectiveness, cost effectiveness and acceptability of VATS vs open surgery for early stage lung cancer. The hypothesis is that VATS surgery is superior to open surgery with respect to self-reported physical function 5 weeks after randomisation (approx. 1 month after surgery). More details can be found at http://www.nets.nihr.ac.uk/projects/hta/130403
Ethics approval(s)	NRES Committee London - Dulwich, 07/01/2015, ref: 14/LO/2129
Condition	Lung cancer (stage cT1a-2b N0-1 M0)
Intervention	Trial participants will be randomised to lobectomy via VATS or open surgery in a 1:1 ratio. Video-assisted thoracoscopic surgery (VATS): VATS lobectomy is undertaken through one to four keyhole incisions without rib spreading. The use of ‘rib spreading’ is prohibited as this is the key intra-operative manoeuvre which disrupts tissues and causes pain (and is used in open surgery). The procedure is performed with videoscopic visualisation without direct vision. The hilar structures are dissected, stapled and divided. Endoscopic ligation of pulmonary arterial branches may be performed. Open surgery: Conventional open surgery is undertaken through a single incision +/- rib resection and with rib spreading. The operation is performed under direct vision with isolation of the hilar structures (vein, artery and bronchus) which are dissected, ligated and divided in sequence and the lobe of lung resected. The procedures may be undertaken using ligatures, over sewing or with staplers. Lymph node management is undertaken in accordance with the International Association of the Study of Lung Cancer (IASLC) recommendations where a minimal of six nodes/stations are removed, of which three are from the mediastinum that includes the subcarinal station. Added 02/04/2019: VIOLET has an embedded sub-study which aims to determine if the presence of molecular residual disease detected in blood samples taken at pre-defined time points after surgery is associated with early cancer recurrence. Consenting participants will have blood drawn at baseline (pre-surgery) and at 5 weeks, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, and 60 months (post-surgery). The blood results of those patients whose cancer returns will be compared to the blood results of those patients who remain cancer-free. The sub-study will continue after recruitment to the main study has finished.
Intervention type	Procedure/Surgery
Primary outcome measure	The primary endpoint is self-reported physical function (QLQ-C30) at 5 weeks post randomisation. Physical function has been chosen because it is a patient-centred outcome that will reflect the anticipated earlier recovery with video-assisted surgery and has been used in other minimal access surgery trials. The primary endpoint has been chosen to be 5 weeks (1 month post-surgery) to capture the early benefits of minimal access surgery on recovery.
Secondary outcome measures	Current secondary outcome measures as of 08/01/2019: 1. Time from surgery to hospital discharge 2. Adverse health events 3. Proportion and time to uptake of adjuvant treatment 4. Proportion of patients upstaged to pN2 disease after the procedure 5. Overall and disease-free survival to 1 year 6. Proportion of patients who undergo complete resection during the procedure 7. Proportion of patients who experience prolonged incision pain (defined as the need of analgesia > 5 weeks after surgery) 8. Generic and disease-specific HRQoL: EORTC QLQ-C30, QLQ-LC13 and EQ5D to 1 year (measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation) 9. Resource use to 1 year (measured for the duration of post-operative hospital stay until discharge, and at 2 weeks, 5 weeks, 3 months, 6 months and 1-year post randomisation) Previous secondary outcome measures: 1. Time from surgery to hospital discharge 2. Adverse health events 3. Proportion and time to uptake of adjuvant treatment 4. Proportion of patients upstaged to pN2 disease after the procedure 5. Overall and disease-free survival to 1 year 6. Proportion of patients who undergo complete resection during the procedure 7. Proportion of patients who experience prolonged incision pain (defined as the need of analgesia > 6 weeks after surgery) 8. Generic and disease-specific HRQoL: EORTC QLQ-C30, QLQ-LC13 and EQ5D to 1 year (measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation) 9. Resource use to 1 year (measured for the duration of post-operative hospital stay until discharge, and at 2 weeks, 5 weeks, 3 months, 6 months and 1-year post randomisation)
Overall study start date	01/01/2015
Overall study end date	01/09/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	498 (Phase 1: 162, Phase 2: 338)
Total final enrolment	503
Participant inclusion criteria	Current participant inclusion criteria as of 08/01/2019: 1. Adults aged ≥16 years of age 2. Able to give written consent, undergoing either: 2.1. Lobectomy or bilobectomy for treatment of known or suspected primary lung cancer beyond lobar orifice* in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 or 2.2. Undergoing frozen section biopsy with the intention to proceed with lobectomy or bilobectomy if primary lung cancer with a peripheral tumour beyond a lobar orifice* in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 is confirmed 3. Disease suitable for both minimal access (VATS) and open surgery Previous participant inclusion criteria: 1. Adults aged ≥16 years of age 2. Able to give written consent, undergoing either: 2.1. Lobectomy for treatment of known or suspected primary lung cancer beyond lobular orifice in stage cT1a-2b N0-1 M0 or 2.2. Undergoing frozen section biopsy with the intention to proceed with lobectomy if primary lung cancer with a peripheral tumour beyond a lobular orifice in stage cT1a-2b N0-1 M0 is confirmed 3. Disease suitable for both minimal access (VATS) and open surgery
Participant exclusion criteria	1. Adults lacking capacity to consent 2. Previous malignancy that influences life expectancy 3. Patients in whom a pneumonectomy or non-anatomic resection (e.g. wedge dissection) is planned 4. Patients with a serious concomitant disorder that would compromise patient safety during surgery 5. Planned robotic surgery
Recruitment start date	01/07/2015
Recruitment end date	01/03/2019

Locations

Countries of recruitment

England
Scotland
United Kingdom

Study participating centres

Royal Brompton Hospital

Sydney Street
London
SW3 6NP
United Kingdom

Harefield Hospital

Hill End Road
Harefield
UB9 6JH
United Kingdom

Bristol Royal Infirmary

Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Liverpool Heart & Chest Hospital

Thomas Drive
Liverpool
L14 3PE
United Kingdom

James Cook University Hospital (Middlesbrough)

Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Oxford University Hospitals - Churchill Hospital

Headley Way
Oxford
OX3 9DU
United Kingdom

Hull and East Yorkshire Hospitals NHS Trust

Castle Road
Cottingham
HU16 5JQ
United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Royal Infirmary of Edinburgh

Little France Crescent
Edinburgh
EH16 4SU
United Kingdom

Sponsor information

Royal Brompton & Harefield NHS Foundation Trust
Hospital/treatment centre

Research Office
Chelsea Wing
Sydney Street
London
SW3 6NP
England
United Kingdom

"ROR"	https://ror.org/02218z997

Funders

Funder type

Not defined

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	31/01/2022
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	A full report will be written for the HTA and the findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. Social media will be used to disseminate and publicise the trial via a website, facebook and twitter streams. The PPI group that work with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Eric Lim (violet-study@bristol.ac.uk). Data will not be made available for sharing until after publication of the main results of the study. 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 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. These identifiers will not be shared with a third party.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	04/10/2019		Yes	No
Results article	results	18/01/2022	27/01/2022	Yes	No
Results article		01/12/2022	19/12/2022	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

26/01/2024: Cancer Research UK plain English summary link was amended.
19/12/2022: Publication reference added.
27/01/2022: Publication reference added.
18/10/2021: The following changes were made to the trial record:
1. The trial website was added.
2, The primary contact was updated.
13/09/2021: The intention to publish date has been changed from 01/09/2021 to 31/01/2022.
16/01/2020: ClinicalTrials.gov number added.
17/10/2019: Publication reference added.
02/04/2019: The following changes were made to the trial record:
1. Total final enrolment number added.
2. Sub-study added to Interventions field - recruitment is paused and due to continue once an amendment has been approved to do so.
11/01/2019: The following changes were made:
1. The publication and dissemination plan was added.
2. The intention to publish date was added.
3. The participant level data was added.
08/01/2019: The following changes were made:
1. The primary contact was updated.
2. The participant inclusion criteria was updated.
3. The secondary outcome measures were updated.
4. The trial participating centres were updated.
24/03/2016: Ethics approval information added.