Condition category
Digestive System
Date applied
27/05/2016
Date assigned
27/05/2016
Last edited
31/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Gallstones are common, especially in women, but in many people they do not cause any symptoms. About one in three people with gallstones develop symptoms (symptomatic). Symptoms usually include a severe pain in the upper right-hand side of the abdomen (known as biliary colic), and sometimes nausea and vomiting. At times the pain is accompanied by inflammation of the gallbladder (cholecystitis). Once gallstones start giving symptoms, painkillers, anti-inflammatory medicines and antibiotics are usually prescribed initially and surgery is advised to medically fit patients. Surgery to remove the gallbladder, known as cholecystectomy, is the most common way to treat biliary pain or cholecystitis due to gallstones. About 70,000 cholecystectomies are performed every year in the UK, with significant costs for the NHS. In the UK, surgery is commonly offered to people who present at secondary care with pain or cholecystitis due to gallstones. However, it is known that some patients do not have any more symptoms after the initial episode of pain and that surgery may not be necessary. A policy of conservative management (painkillers/antibiotics and lifestyle advice) could therefore be appropriate in this group of people. A review of current evidence suggested that conservative management may provide a more efficient use of NHS resources. There were, however, great uncertainties in the data, with only two small studies run in Norway. There is a need for a definitive study to address these uncertainties. The aim of this study is to find out whether there any differences between conservative management and cholecystectomy in terms of patient quality of life and cost-effectiveness.

Who can participate?
Adult patients with symptomatic gallstone disease

What does the study involve?
Participants randomly allocated to either receive a surgical procedure to remove the gallbladder or to receive conservative management. Apart from treatment allocation and measurement of study outcomes, participants receive standard NHS follow up for at least 18 months. The main outcome of the study is the effect of the two policies on the participants’ quality of life. We assess this using a questionnaire. To assess any longer term benefits of either policy we use a mathematical model to give a prediction of quality of life over each participant’s lifetime. We use the measurements we collect and the model to work out whether gall bladder removal is worthwhile to the NHS in terms of balancing any benefit to people’s health against the added costs (cost-effectiveness).

What are the possible benefits and risks of participating?
Patients receive the same health care whether or not they choose to participate in the study. By taking part, they will be directly helping us to inform the future treatment of people with uncomplicated gallstones. The results of this study will help plan effective services offered by the NHS in the future. Risks and complications are possible from both surgical treatment and “watchful waiting” and participation in this study should not increase those risks. There are risks associated with surgical procedures and anaesthetics.

Where is the study run from?
1. NHS Grampian (UK)
2. Taunton and Somerset NHS Foundation Trust (UK)
3. Nottingham University Hospital NHS Trust (UK)

When is the study starting and how long is it expected to run for?
April 2016 to October 2020

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
Karen Innes
kareninnes@abdn.ac.uk

Trial website

https://w3.abdn.ac.uk/hsru/C-GALL/

Contact information

Type

Public

Primary contact

Miss Karen Innes

ORCID ID

Contact details

CHaRT
HSRU
3rd Floor Health Sciences Building
University of Aberdeen
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom
+44 (0)1224 438089
kareninnes@abdn.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version 2.0, 20/05/2016; HTA 14/192/71

Study information

Scientific title

A randomised controlled trial comparing laparoscopic cholecystectomy with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones

Acronym

C-Gall

Study hypothesis

Is there any difference between observation/conservative management and cholecystectomy in terms of participant quality of life and cost-effectiveness in terms of incremental cost per QALY?

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/1419271

Ethics approval

North of Scotland Research Ethics Service (Committee 2), 23/05/2016, ref: 16/NS/0053

Study design

Pragmatic multi-centre parallel-group patient randomised superiority trial (with internal pilot phase)

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

https://w3.abdn.ac.uk/hsru/C-GALL/

Condition

Gallstones

Intervention

1. Laparoscopic cholecystectomy: the current standard surgical procedure for the management of symptomatic gallstone disease. The gall bladder is removed with the stones within it using keyhole techniques (laparoscopy). The procedure is undertaken under a general anaesthetic. It usually involves three to four small incisions in the abdomen, which allow the surgeon to dissect the gallbladder from its attachments and safely divide the key anatomical structures (the cystic duct and artery) that link it to the biliary tree. The gallbladder is then separated from the under surface of the liver. Usually the gallbladder (containing the stones) is removed within a retrieval bag via one of the small incisions. The operation takes between 45 and 120 minutes, many patients are admitted for one night, although day case laparoscopic cholecystectomy is safely undertaken in an otherwise fit patients with appropriate social support.

2. Observation/conservative management: observation/conservative management in the context of gallstone disease involves the prescription of analgesics to relieve the biliary pain. Typical therapy includes paracetamol, antispasmotics (e.g. Buscopan), nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen etc), narcotic analgesics (e.g. opiates) together with generic lifestyle advice. In the longer term, conservative management also may involve these strategies for symptom management if required, as well as advice to eat a healthy diet with regular meals (http://www.nhs.uk/Conditions/Gallstones/Pages/Treatment.aspx). For the purpose of this trial a standard protocol for conservative management will be agreed with the PPI group and used in all centres. Safety advice for patients in the observation/conservative management group will be aligned with the current advice given via the NHS choice website (www.nhs.uk).

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

The primary patient outcome measure will be quality of life as measured by area under the curve (AUC) at up to 18 months post-randomisation using the SF-36 bodily pain domain (AUC measures at 3, 9 and 18 months).

The primary economic outcome measure will be incremental cost per QALY.

Secondary outcome measures

Measured at baseline, 3, 9, 12 and 18 months:
1. Condition-specific quality of life (CSQ – The Otago gallstone condition specific questionnaire)
2. SF-36 domains (excluding bodily pain domain) complications
3. Need for further treatment
4. Persistent symptoms
5. Healthcare resource use
6. Costs

In addition, routinely collected national data on further surgery will be sought in the future to update longer term estimates of cost-effectiveness.

Overall trial start date

01/04/2016

Overall trial end date

01/10/2020

Reason abandoned

Eligibility

Participant inclusion criteria

All adult patients with confirmed gallstones electively referred to a secondary care setting for consultation.

Clinical diagnosis of gallstone disease will be confirmed by imaging. Transabdominal ultrasonography is the standard imaging technique for the diagnosis of gallbladder stones, but diagnosis by any imaging technique is acceptable.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

430

Participant exclusion criteria

1. Unable to consent
2. ASA III and above
3. Pregnancy
4. Previous open major upper abdominal surgery
5. Gallstones in common bile duct or evidence of previous choledocholithiasis
6. A history of acute pancreatitis
7. Abnormal liver function tests (with the exception of GGT <90u/L)
8. Evidence of empyema of the gallbladder
9. Perforated gallbladder
10. Haemolytic disease

Recruitment start date

01/09/2016

Recruitment end date

01/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NHS Grampian
Department of Surgery Aberdeen Royal Infirmary Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Taunton and Somerset NHS Foundation Trust
Department of Surgery Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Nottingham University Hospital NHS Trust
Department of Surgery
Nottingham
NG7 2UH
United Kingdom

Sponsor information

Organisation

University of Aberdeen (UK)

Sponsor details

Research Governance Office
Room 7
Foresterhill Annexe
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom

Sponsor type

University/education

Website

Organisation

Grampian Health Board (UK)

Sponsor details

Research and Development Office
Foresterhill Annexe
Foresterhill
Aberdeen
AB25 2ZD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

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

To be confirmed at a later date

Intention to publish date

01/04/2021

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes