A controlled clinical trial investigating the clinical and cost-effectiveness of early Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPSS) procedure to insert a stent (tube) in the liver to reduce pressure versus endoscopic plus drug therapy in patients with cirrhosis and acute variceal bleeding after initial control of bleeding by variceal band ligation (VBL)
| ISRCTN | ISRCTN85274829 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85274829 |
| Secondary identifying numbers | CPMS 54613, IRAS 314108/327501 |
- Submission date
- 15/06/2023
- Registration date
- 30/06/2023
- Last edited
- 09/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Cirrhosis (scarring of the liver) can lead to varices (abnormally enlarged veins) developing in the lower gullet (food pipe) or stomach causing the varices to bleed. Variceal bleeding is a serious complication of liver cirrhosis. The currently accepted treatment for patients who bleed from varices is known as the standard of care (SOC) and includes using an endoscope (a bendy tube incorporating light and a tiny video camera) to tie off an enlarged vein with a rubber ring (variceal banding) or injecting a drug, with a needle, directly into the swollen vein, causing the vein to clot and stop the bleeding. Patients may also be prescribed antibiotics and other drugs like beta-blockers to lower pressure in the enlarged veins to reduce the risk of further bleeding. For some patients, a device called a transjugular intrahepatic portosystemic stent-shunt (TIPSS) is used. The TIPSS procedure involves placing a special small metal tube, roughly 10mm in diameter, inside the liver using a wire passed through a vein in the neck and down through the liver. The procedure is done under sedation or general anaesthetic. TIPSS may be used to treat severe variceal bleeding in an emergency to stop bleeding where SOC has not worked or in patients that are at high risk of bleeding again after satisfactory stabilisation with SOC. This is called “early” TIPSS. The REACT-AVB trial will compare “early” TIPSS with SOC in severe variceal bleeding patients to see if “early” TIPSS treatment is better than SOC in improving the survival of these patients. It will also compare cost-effectiveness and quality of life for the patients for both treatments. REACT-AVB will be recruiting patients from hospitals throughout the UK.
Who can participate?
Patients, aged 18 years and over who have liver cirrhosis and have been admitted to the hospital with variceal bleeding and have undergone an emergency endoscopy procedure for gastrointestinal bleeding
What does the study involve?
Once the patient has consented they will be randomly selected by a computer to one of the treatment arms. The treatment will continue for at least one year.
During the trial, patients will be seen at 3 separate time points, 6 weeks, 6 and 12 months (these normally coincide with their usual standard appointments) to assess their health. Patients will also be asked, by a research nurse to complete a health questionnaire form, (EQ5D-5L) on three separate occasions.
What are the possible benefits and risks of participating?
Whilst there is no guarantee that there will be any direct benefit to the patient, by taking part in the trial, they may feel empowered knowing that their contribution to the results of the trial should in the future, lead to the best treatment for variceal bleeding in patients with liver cirrhosis.
The TIPSS procedure has been in use for over 30 years and carries few complications. Variceal banding has been used for over 30 years and is generally considered very safe. For further details, please refer to the patient information sheet which can be accessed via the trial website https://www.birmingham.ac.uk/react-avb.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
December 2021 to November 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
Mrs Sukhi Sehmi (REACT-AVB Senior Trial Manager), S.sehmi@bham.ac.uk (UK)
Contact information
Principal Investigator
Room 01, 1st Floor West
Institute of Translational Medicine
Heritage Building
Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
 ORCID ID |
0000-0001-9043-6382 |
|---|---|
| Phone | +44 (0)121 371 4672 |
| dhiraj.tripathi@uhb.nhs.uk |
Public
Birmingham Clinical Trials Unit
Birmingham
-
United Kingdom
| Phone | None available |
|---|---|
| react-avb@trials.bham.ac.uk |
Scientific
Senior Trial Manager
University of Birmingham
Birmingham Clinical Trials Unit
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 415 8445 |
|---|---|
| s.sehmi@bham.ac.uk |
Study information
| Study design | Randomized interventional treatment device imaging study |
|---|---|
| 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 below to request a patient information sheet |
| Scientific title | Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in Acute Variceal Bleeding (REACT-AVB) |
| Study acronym | REACT-AVB |
| Study objectives | Early transjugular intrahepatic portosystemic stent-shunt (TIPSS) within 4 days of acute variceal bleed results in improved transplant-free patient survival when compared with standard of care |
| Ethics approval(s) |
1. Approved 29/09/2023, Scotland A Ethics Committee (NHS Lothian, Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, United Kingdom; None available; Manx.Neill@nhslothian.scot.nhs.uk), ref: 23/SS/0050 2. Approved 04/07/2023, West Midlands - Coventry & Warwickshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 (0)207 104 8009; coventryandwarwick.rec@hra.nhs.uk), ref: 23/WM/0085 |
| Health condition(s) or problem(s) studied | Complications of cirrhosis |
| Intervention | Cirrhosis (scarring of the liver) can lead to varices (abnormally enlarged veins) developing in the lower gullet (food pipe) or stomach. Variceal bleeding is a serious complication of liver cirrhosis. Patients with variceal bleeding need treatment with one of the following: • Medicines (beta-blockers which slow down the heart and lower pressure in the enlarged veins, this reduces the risk of further bleeding) and endoscopic treatment (using a bendy tube incorporating light and a tiny video camera to tie off varices with rubber bands or inject a drug) to stop the bleeding and prevent further bleeding. This is known as standard of care (SOC). • For patients at high risk of bleeding again, an “early” Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPSS) is offered to reduce the risk of further bleeding. The TIPSS procedure involves placing a special small metal tube, roughly 10mm in diameter (about the size of a grain of rice), inside the liver using a wire passed through a vein in the neck and down through the liver. The procedure is done under sedation (you will be sleepy) or general anaesthetic (you will be asleep). The procedure is done with X-ray imaging guidance. There have only been a few clinical trials comparing early TIPSS with SOC in a small number of patients. The results from these trials are not clear as to which patients benefit from early TIPSS and whether it works. Current guidelines recommend further research. Nobody so far has compared early TIPSS with SOC in a large clinical trial and obtained clear results. This trial is being conducted to find out if early TIPSS is better than SOC. This trial will randomly assign (like flipping a coin) patients to either SOC or early TIPSS to avoid any bias and ensure patients in both treatment groups are well matched and similar. Once the treatment group (either SOC or early TIPSS) is assigned, the participant and research staff will know which treatment have been given. Potential participants with liver cirrhosis and admitted to the hospital with bleeding from varices will be invited to take part and given a patient information sheet to read. The decision to take part in the trial will be entirely voluntary. If a patient decides to participate, the research staff will ask the patient to read and sign the consent form. The signed consent form will stay on record in the participant's trial file and medical records and be available for review by the trial monitors. A copy will also be given to the participant and with their permission, a copy will also be sent to the REACT-AVB Trial Office at the University of Birmingham. During the trial, participants will be asked to confirm their willingness to continue in the trial. If they decide not to take part, their normal treatment will not be affected in any way and they will continue to be cared for by your normal care team who will ensure that they receive treatment for bleeding varices. Where potential participants are critically ill and lack the capacity to consent for themselves because of sedation, infection and delirium, advice will be sought from a consultee (for sites in England, Wales and Northern Ireland) or consent will be sought from a legal representative (for sites in Scotland). When the participant regains capacity during the study, the site will need to confirm ongoing consent at the earliest opportunity. To protect the interest of patients, no trial procedure will take place until advice/consent has been sought. During the trial, at 3 separate time points (baseline, 6 months, and 12 months), participants will be asked to complete a health questionnaire form, (EQ5D-5L). This may be carried out face-to-face with the research staff or remotely. With permission from the participant, a copy of the completed form will also be sent to the REACT-AVB Trial Office. All patients who take part in the trial will be seen as usual clinical practice either in the clinic or over the telephone/video conference, every few months to assess well-being and to look for untoward effects. Patients in the early TIPSS group will have an ultrasound to check that the TIPSS is working well on 2-7 days. These patients do not require further endoscopies or beta-blockers. Patients in the SOC group will be prescribed regular beta-blockers and have endoscopies to treat the varices every few weeks to months depending on how well the varices respond to treatment. The trial will seek to recruit just under 300 patients nationally over 4 years. It includes a 12-month pilot trial to address any problems early. The trial will also compare cost-effectiveness and quality of life for the patients for both treatments. If it is concluded that early TIPSS is more effective in terms of survival, cost, and quality of life than SOC, this could lead to a major change in clinical practice. |
| Intervention type | Other |
| Primary outcome measure | Transplant-free survival measured using the discharge and follow-up forms at one year (post-randomisation) |
| Secondary outcome measures | Current secondary outcome measures as of 10/07/2023: 1. Transplant-free survival measured using the discharge and follow-up forms at 6 weeks (post-randomisation) 2. Rebleeding* measured using the discharge and follow-up forms (post-randomisation): 2.1. Early (less than or equal to 6 weeks) 2.2. Late (greater than 6 weeks) 3. Serious adverse events (SAE) related to treatment measured using the SAE form (up to 12 months post-randomisation) 4. Other complications of cirrhosis measured using the discharge and follow-up forms (up to 12 months post-randomisation): 4.1. New onset ascites 4.2. New onset encephalopathy 4.3. Spontaneous bacterial peritonitis 4.4. Hepatocellular carcinoma 4.4. Any renal dysfunction 5. Mortality prediction measured using Child-Pugh scoring at 6 and 12 months (post-randomisation) 6. Survival prediction measured using the Model for End-Stage Liver Disease (MELD) scoring at 6 and 12 months (post-randomisation) 7. Health-related quality of life measured using the EuroQol EQ-5D-5L at 6 and 12 months (post-randomisation) 8. Use of healthcare resources, costs and cost-effectiveness based on cost per Quality-Adjusted Life-Year (QALY) estimated measured using the EQ-5D-5L and cost per life year gained at one year, and modelled cost per QALY over a patient lifetime 9. Crossover therapies measured using the discharge and follow-up forms up to 12 months post-randomisation *Rebleeding is defined as hematemesis and/or melena with either: 1. Endoscopic evidence of variceal bleeding or stigmata of recent haemorrhage and at least a 2 g/L reduction in haemoglobin within 24 hours of admission 2. Massive upper gastrointestinal bleeding leading to death. The definition includes bleeding from banding ulceration. _____ Previous secondary outcome measures: 1. Transplant-free survival measured using the discharge and follow-up forms at 6 weeks (post-randomisation) 2. Rebleeding* measured using the discharge and follow-up forms (post-randomisation): 2.1. Early (within 6 weeks) 2.2. Late (6 weeks to 1 year) 3. Serious adverse events (SAE) related to treatment measured using the SAE form (up to 12 months post-randomisation) 4. Other complications of cirrhosis measured using the discharge and follow-up forms (up to 12 months post-randomisation): 4.1. New onset ascites 4.2. New onset encephalopathy 4.3. Spontaneous bacterial peritonitis 4.4. Hepatocellular carcinoma. 4.4. Any renal dysfunction 5. Mortality prediction measured using Child-Pugh scoring at 6 and 12 months (post-randomisation) 6. Survival prediction measured using the Model for End-Stage Liver Disease (MELD) scoring at 6 and 12 months (post-randomisation) 7. Health-related quality of life measured using the EuroQol EQ-5D-5L at 6 and 12 months (post-randomisation) 8. Use of healthcare resources, costs and cost-effectiveness based on cost per Quality-Adjusted Life-Year (QALY) estimated measured using the EQ-5D-5L and cost per life year gained at one year, and modelled cost per QALY over a patient lifetime 9. Crossover therapies measured using the discharge and follow-up forms up to 12 months post-randomisation *Rebleeding is defined as hematemesis and/or melena with either: 1. Endoscopic evidence of variceal bleeding or stigmata of recent haemorrhage and at least a 2 g/L reduction in haemoglobin within 24 hours of admission 2. Massive upper gastrointestinal bleeding leading to death. The definition includes bleeding from banding ulceration. |
| Overall study start date | 01/12/2021 |
| Completion date | 30/11/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 294; UK Sample Size: 294 |
| Key inclusion criteria | 1. Liver cirrhosis as defined clinically, radiologically (ultrasound scan (USS) and/or transient elastography) or on histology 2. Acute variceal bleed (oesophageal or gastric) with haemostasis following initial endoscopic therapy 3. Child-Pugh score 7-13 4. Age > = 18 years |
| Key exclusion criteria | 1. Failure to control acute bleeding (as per Baveno 7 criteria) prior to randomisation. 2. Previous portosystemic shunt or TIPSS. 3. Known occlusive portal vein thrombosis precluding TIPSS. 4. Active cancer including hepatocellular carcinoma affecting 1-year survival. 5. Clinically significant encephalopathy causing recurrent hospital admissions. 6. Pregnant or lactating women. 7. Evidence of heart failure refractory to treatment. 8. Severe active septicaemia refractory to treatment. |
| Date of first enrolment | 08/03/2024 |
| Date of final enrolment | 30/09/2027 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Edgbaston
Birmingham
B15 2GW
United Kingdom
London
NW3 2QG
United Kingdom
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
Glasgow
G4 0SF
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Nottingham
NG7 2UH
United Kingdom
London
N19 5NF
United Kingdom
Derriford
Plymouth
PL6 8DH
United Kingdom
Glasgow
G51 4TF
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Sutton Coldfield
B75 7RR
United Kingdom
C Floor, Huntsmnan Building
Herries Road
Sheffield
S5 7AU
United Kingdom
Bordesley Green
Birmingham
B9 5ST
United Kingdom
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Sandford Road
Cheltenham
GL53 7AN
United Kingdom
Sponsor information
University/education
C/o: Dr Birgit Whitman
Research Park
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)7814 650003 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
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 | 30/05/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | The results of the REACT-AVB trial will be disseminated via publication in high-impact peer-reviewed journals. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. The trial data will be entered into a secure trial-specific database and data will not be publicly available prior to publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 22/03/2024 | 25/03/2024 | Yes | No |
Editorial Notes
09/04/2025: The study participating centres John Radcliffe Hospital, Queen's Medical Centre , The Whittington Hospital, Derriford Hospital, Queen Elizabeth University Hospital , Norfolk and Norwich University Hospital, Good Hope Hospital, Northern General Hospital, Heartlands Hospital , Southmead Hospital , Gloucestershire Hospitals NHS Foundation Trust, Gloucestershire Hospitals NHS Foundation Trust were added.
25/03/2024: Publication reference added.
12/03/2024: The recruitment start date was changed from 28/02/2024 to 08/03/2024.
08/03/2024: The recruitment start date was changed from 30/09/2023 to 28/02/2024.
02/10/2023: The ethics approval from Scotland A Ethics Committee was added.
13/09/2023: The recruitment start date was changed from 01/09/2023 to 30/09/2023.
10/07/2023: The following changes were made to the trial record:
1. The ethics approval from West Midlands - Coventry & Warwickshire Research Ethics Committee was added.
2. The secondary outcome measures were changed.
15/06/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
