Condition category
Surgery
Date applied
24/09/2018
Date assigned
02/10/2018
Last edited
02/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Surgery to remove the gallbladder is required if it contains gallstones that cause problems. About 70,000 operations are performed annually in England. Sometimes, gallstones cause other problems if they pass from the gallbladder into the nearby bile duct (e.g. jaundice/inflammation of the pancreas). If this happens, it is necessary to remove the bile duct stones before or during the gallbladder operation. Because of this, patients requiring gallbladder surgery are assessed for any risk of bile duct stones. If the risk is high, further tests are done to identify if bile duct stones are present. If the risk is moderate or low (although it can be difficult to distinguish between the two), then it is uncertain whether further tests to look for bile duct stones are necessary. As a result, some surgeons choose to perform tests and others don’t. A UK-wide research study found that a third of patients undergoing gallbladder surgery were tested, usually before surgery using an MRI scanner. This test, called a Magnetic Resonance Cholangiopancreatography (MRCP), involves a 1-hour visit to hospital and costs the NHS about £365. The MRCP identifies bile duct stones but may delay gallbladder surgery which can lead to increased problems with gallstones whilst waiting. There are other uncertainties about the need for testing using MRCP. Even if the MRCP shows bile duct stones, the stones can pass into the bowel spontaneously; and removing the stones can cause complications. Not having the MRCP avoids these risks, but can lead to bile duct stones being left behind after surgery, which may also cause complications. Research to establish if going straight to gallbladder surgery without testing the bile duct beforehand is needed.
The Sunflower Study will find out whether testing for bile duct stones with MRCP before gallbladder surgery is worthwhile or not in patients with a low or moderate risk of having stones.

Who can participate?
Adults with symptomatic gallstone disease who are scheduled and fit to receive gallbladder surgery, with a low to moderate risk of common bile duct stones

What does the study involve?
Participants in the Sunflower study will be divided into two groups. One group will go straight to surgery (i.e. no additional testing) and the other will receive an MRCP before surgery. The groups will be selected by a process called randomisation to ensure that groups have similar patients in terms of factors such as general health, age and gender. The ‘straight to surgery’ group will have twice as many people in as the ‘tested’ group to reduce the number of extra MRCPs performed. Both groups will be followed for 18 months and information about the need for treatment of bile duct stones, complications of surgery and costs collected.

What are the possible benefits and risks of participating?
For participants who receive MRCP, the possible benefit of participating is that this procedure may detect and, if needed, treat problematic bile duct stones. However for participants who do not receive MRCP, the possible benefit is that this allows their gallbladder surgery to go ahead immediately, without the possible disadvantages of testing for bile duct stones.
For participants who receive MRCP, the possible risks of participating is that the procedure may be unnecessary, as bile duct stones often pass safely and spontaneously into the bowel. Additionally, in 10-20% of cases, MRCP may not detec bile duct stones. Additionally, some patients may experience claustrophobia during the scan. For some patients, the scan and endoscope procedure (if required) may lead to a longer wait time for gallbladder surgery, which can lead to problems with gallstones whilst waiting (however, the surgery may not always be delayed by this).
For participants who do not receive MRCP, the possible risk is that any bile duct stones present will not be detected, which could lead to problems after gallbladder surgery (i.e. jaundice, infection, pancreatitis) and therefore require further treatment or readmission to hospital. If bile duct stones are suspected later, a scan and potentially endoscope procedure will be likely needed to remove them.

Where is the study run from?
Leeds Teaching Hospitals NHS Trust and at least 50 hospitals throughout the UK.

When is the study starting and how long is it expected to run for?
January 2018 to May 2024

Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment Programme (UK)

Who is the main contact?
Madeleine Clout
sunflower-study@bristol.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Madeleine Clout

ORCID ID

http://orcid.org/0000-0001-7645-1199

Contact details

Research Floor Level 7
Queens Building
Bristol Royal Infirmary
Marlborough Street
Bristol
BS2 8HW
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16/142/04

Study information

Scientific title

The Sunflower Study: A randomised controlled trial to establish the clinical and cost effectiveness of expectant management versus pre-operative imaging with MRCP in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones

Acronym

The Sunflower Study

Study hypothesis

We will test the hypothesis that expectant management is non-inferior to magnetic resonance pancreaticogram (MRCP) with respect to hospitalisation for treatment for a complication of gallstones up to 18 months after randomisation.

Ethics approval

Submitted to Yorkshire & The Humber - South Yorkshire Research Ethics Committee, 27/09/2018

Study design

Interventional multi-centre pragmatic randomised controlled trial with an internal pilot phase (Phase
I) and a quintet recruitment intervention (QRI).

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participation information sheet

Condition

Symptomatic gallbladder disease, requiring gallbladder surgery

Intervention

Participants will be randomly allocated in a 1:2 ratio to receive either a reoperative magnetic resonance pancreaticogram (magentic resonance cholangiopancreatography - MRCP) or no MRCP (expectant management) using an online system.
In the MRCP arm, participants will undergo an MRCP prior to their gallbladder surgery. An MRCP takes on average 20-30 minutes. In the expectant management arm, participants will proceed directly to surgery without undergoing an MRCP. The follow up will be the same in both groups – a 20% sample will be asked to complete questionnaires at 3, 6, 12 and 18 months post randomisation.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Any of the following:
1. Any hospital admission within 18 months of randomisation for treatment of complications of gallstones whether in the CBD or gallbladder
2. Complications during the admission for LC for the treatment for gallstones or readmission for complications of the LC. Complications comprise:
2.1. Return to theatre post LC for any cause
2.2. Percutaneous radiological drainage
2.3. ERC
3. Complications during the index admission for ERCP for the treatment for gallstones (i.e. an ERCP performed following an MRCP where CBD stones were identified). Complications comprise:
3.1. Blood transfusion post ERCP
3.2. Percutaneous radiological drainage
3.3. Further ERCP
3.4. Treatment of a perforation occurring during ERCP
3.5. Acute pancreatitis
3.6. Respiratory complications leading to extended hospital stay of > 2 days
3.7. Cardiac complications leading to extended hospital stay of > 2 days
3.8. Infective complications leading to extended hospital stay of > 2 days
3.9. Other complications leading to extended hospital stay of > 2 days (detail to be recorded).
This will be acquired from routine data sources, such as HES data from NHS Digital in England. The HES data will be reviewed and specific OPCS-4 and ICD-10 codes will be searched for. These codes identify specific diagnoses, procedures, etc which will form the primary outcome measure. This will be measured in the 18 months following randomisation.

Secondary outcome measures

1. Health-related quality of life, assessed using the EQ-5D-5L questionnaire at time of randomisation, admission for LC and 3, 6, 12 and 18 months after randomisation (participants will not be asked to complete the admission for LC questionnaire if they have completed their baseline questionnaire within the previous two days)
2. Items in the LC core outcome set, which is due to be published at the end of 2018
3. NHS resource use to 18 months post randomisation, taken from routine data sources such as HES data from NHS Digital in England

Overall trial start date

01/01/2018

Overall trial end date

31/05/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged 18 years or older
2. Symptomatic gallstone disease, confirmed by trans-abdominal ultrasound scan (USS) or computed tomography (CT) scan, including:
2.1. Biliary colic
2.2. Cholecystitis
2.3. Mild and severe pancreatitis
2.4. Gallbladder polyps
2.5. Gallbladder dyskinesia
3. Scheduled and fit for laparascopic cholecystectomy (LC) as an elective or urgent procedure
4. Low or moderate risk of common bile duct (CBD) stones, including all of the following:
4.1. CBD diameter ≤8 mm on USS
4.2. Bilirubin ≤ 50umol/l
4.3. Alanine transferase less than twice the upper limit of normal (≤2 x ULN) and/or alkaline phosphatase ≤2 x ULN.
If a patient does not meet the definition of low or moderate risk of CBD stones solely because both alanine transferase and alkaline phosphatase are > 2 x ULN, if repeat blood tests are carried out and at least one of the second or subsequent test results is within range (i.e. ≤ 2 x ULN) the patient may be recruited at that time.
If a patient does not meet the definition of low or moderate risk of CBD stones solely because bilirubin > 50umol/l, if repeat blood tests are carried out and at least one of the second or subsequent test results is within range the patient may be recruited at that time.
If CBD cannot be seen on USS or CT scan, the patient may be recruited as long as all the other inclusion criteria are met and there is no intrahepatic duct dilatation reported.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

13,680

Participant exclusion criteria

1. Unable to undergo MRCP
2. Evidence of empyema or perforated gallbladder requiring urgent intervention
3. Previous duodenal bypass
4. Previous MRCP within last 3 months
5. Haemolytic disease
6. Pregnancy
7. Unwilling to participate in follow up
8. Unable to provide written informed consent
9. Prisoner

Recruitment start date

01/12/2018

Recruitment end date

30/11/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
LS1 3EX
United Kingdom

Sponsor information

Organisation

Leeds Teaching Hospitals NHS Trust

Sponsor details

Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The data from this study will be used to produce outputs including publications in peer-reviewed academic journals, and presentations at national and international conferences. A simplified version of the findings will also be disseminated as newsletters to patients, in accordance with advice from the PPI group about how best to do this effectively.
A report to the funding body (HTA) will be sent to the NIHR in May 2024, and will provide a summary of the work undertaken during the life of the study. The target journals for the main study paper and other related publications (e.g. health economics, qualitative) have not been identified, but these will be Open Access and should be completed by early 2025. These will communicate the results of the primary and secondary outcomes of the study. The main study paper should be published in Summer 2024. A summary for stakeholders will be provided in late 2024, and will be aimed both externally (e.g. general public/patients, media, commissioners) and internally (e.g. participating Trust stuff, operational staff). All outputs will be reviewed by the Chief Investigator and other collaborators, as necessary.
Findings will be shared with the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) and the Great Britain and Ireland Hepato Pancreato Biliary Association (GBIHPBA). The Chief Investigator and co-applicants have close links with these groups who are already aware and supportive of the study and awaiting its results. The study team intend to make presentations to both of them. Presentations will be given at national and international conferences relevant to gallbladder surgery e.g. The International Hepatopancreatobiliary Association and other sister Societies (e.g. European and African Hepatopancreatobiliary Association and the American Hepatopancreatobiliary Association). We expect that the results of the study will be used by NHS England to formulate a commissioning policy and will inform national and international guidelines.

IPD sharing statement:
Data requests would be sent to the study manager via sunflower-study@bristol.ac.uk. The full de-identified dataset would be available and will be held indefinitely. Access would be dependent on provision of an ethically approval study protocol and could cover numerous analysis types. The mechanism of data sharing would be determined at the time. Consent from participants will be obtained for data sharing. Data will be de-identified. Ethical approval for a new project would need to be in place.

Intention to publish date

31/05/2024

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes