Home versus hospital drainage of fluid from the abdomen (ascites) for patients with advanced cirrhosis
| ISRCTN | ISRCTN26993825 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN26993825 |
| IRAS number | 314073 |
| Secondary identifying numbers | CPMS 52988, IRAS 314073 |
- Submission date
- 28/07/2022
- Registration date
- 15/08/2022
- Last edited
- 04/12/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English Summary
Background and study aims
The liver can be damaged (scarred) by excessive alcohol and viral infections. If liver damage continues, this scarring leads to permanent damage (cirrhosis). As cirrhosis progresses, it causes a painful buildup of fluid (ascites) in the belly (abdomen). Initially, drugs can treat ascites, but these may stop working, leading to untreatable ascites. A liver transplant is then the best option. Most people, however, do not receive a transplant due to concerns about their alcohol use or lack of donors.
People with cirrhosis and untreatable ascites who do not receive a liver transplant live on average for about six months. Medical care then focuses on controlling symptoms and having the best possible quality of life. This is known as palliative care. Current standard palliative care for untreatable ascites involves coming into the hospital for 1-2 days, putting a thin tube into the abdomen for a few hours and draining 5-15 L of fluid. This reduces the pain from ascites. However, as the ascites build up quickly, hospital visits are needed every 10-14 days. Our patients describe repeated hospital drainage as ”devastating” and “unbearably painful”.
For people with untreatable ascites due to cancer (rather than cirrhosis), palliative care involves placing another tube, a long-term abdominal drain (LTAD), into their abdomen. This tube is fitted in the hospital but stays in place for months. Nurses/caregivers then drain smaller amounts of fluid (1-2 L) up to three times a week in the community. LTADs avoid frequent hospital visits and can improve their quality of life.
LTADs are not routinely offered to people with cirrhosis as they can have complicated social issues like addiction, making community care difficult. Secondly, people with cirrhosis are at increased risk of ascitic fluid infection. The concern is that LTADs might further increase this risk. It remains uncertain, therefore, if LTADs could improve the quality of life for people with cirrhosis.
We ran a small study (2015-18) with 36 patients with cirrhosis and untreatable ascites. Half received LTADs and half continued with standard hospital drainage. LTAD insertion went well with no major complications. Almost all with LTAD were managed in the community with lower overall costs compared with hospital drainage. Participants were willing to fill in study questionnaires and take part in interviews. Patients and clinical staff told us that LTADs were acceptable to them.
We are now running a larger study to understand the risks/benefits of palliative LTADs in people with cirrhosis. Our aim is to see if palliative LTADs result in a better quality of life in patients with fluid in the abdomen due to liver scarring, compared with the current standard of care.
Who can participate?
Patients with advanced cirrhosis and untreatable ascites if a liver transplant is not an option
What does the study involve?
In this study, people who agree to take part will have ascites drained through either LTAD or repeated hospital visits. Community nurses will visit LTAD patients at home up to three times a week for ascites drainage. Researchers will visit ALL participants at home every 2 weeks for 12 weeks for safety monitoring and also record the quality of life, symptoms, carer workload and use of NHS services (using questionnaires). We will record all infections that occur. We will talk with patients/caregivers/clinical staff to ask for their views about the research. The most important measure chosen to see if LTAD is a good option for people with cirrhosis is quality of life. The study has been designed with help of the patients/caregivers who are part of the research team.
What are the possible benefits and risks of participating?
There may be no direct benefits to patients. Information collected about patients taking part in this study will help us determine whether home drains are a suitable option for people with cirrhosis and if so, whether they improve quality of life. The complications observed in the LTAD group are similar to that seen in the hospital drain group, except leakage and inflammation around the drain site were higher in the home drain group (about 40 in 100 people versus about 11 in 100 people). Draining ascites to dryness in the hospital after insertion of LTAD can reduce leakage and this is now our standard practice.
Where is the study run from?
University Hospitals Sussex NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
May 2022 to September 2026
Who is funding the study?
National Institute for Health and Care Research (NIHR)
Who is the main contact?
Prof Sumita Verma (Chief Investigator) (UK)
Contact information
Principal Investigator
University of Sussex
Brighton and Sussex Medical School
Main Teaching Building
Room 2.17
Falmer
Brighton
BN1 9PX
United Kingdom
 ORCID ID |
0000-0001-7021-8409 |
|---|---|
| Phone | +44 (0)1273 877890 |
| s.verma@bsms.ac.uk |
Public
Clinical Trial Manager
Brighton & Sussex Clinical Trials Unit
Room 111, Watson Building
University of Brighton
Brighton
BN1 9PH
United Kingdom
| Phone | None provided |
|---|---|
| a.porges@bsms.ac.uk |
Study information
| Study design | Randomized interventional multi-centre non-blinded parallel-group |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community, Hospital |
| Study type | Treatment, Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Palliative long-term abdominal drains versus repeated drainage in untreatable ascites due to advanced cirrhosis: A randomised controlled trial (REDUCe 2 study) |
| Study acronym | REDUCe 2 |
| Study hypothesis | Palliative long-term abdominal drains, by moving care to the community, will result in a better quality of life compared with hospital drainage in patients with refractory ascites due to advanced cirrhosis |
| Ethics approval(s) |
Approved 29/06/2022, South Central - Oxford C Research Ethics Committee Health Research Authority (Ground Floor, Temple Quay House, 2 The Square, Bristol, BS1 6PN, United Kingdom; +44(0)207 1048241; oxford.rec@hra.nhs.uk), ref: 22/SC/0164 |
| Condition | Complications of cirrhosis |
| Intervention | Current interventions as of 01/11/2023: Study design This RCT will follow on from the REDUCe feasibility study and will compare the insertion of a palliative tunnelled long-term abdominal drain (LTAD) (Group 1 intervention) to the standard of care (large volume paracentesis (LVP) (Group 2) in the management of refractory ascites due to advanced cirrhosis. This multi-centre, non-blinded parallel-group RCT with up to 3 months of follow-up will be conducted across 35 sites in England, Scotland and Wales. We aim to recruit 310 patients. 30 patients, 20 informal caregivers and 20 healthcare professionals will also be invited to give their perceptions/perspectives of LTAD and LVP using qualitative methods. The study will commence recruitment in October/November 2022 and is due to be completed in September 2026 which is the last patient last visit (LPLV). We have built in a 6-month lead-up time to secure HRA approvals and ensure all sites are set up and appropriate training provided. After the LPLV we have time to ensure the dataset is clean and locked for the statisticians to undertake the analysis. These timelines have been reviewed and approved by the funder: NIHR HTA. Participants will be approached by a member of the clinical team and provided with information about the study. The sample size has been calculated using HRQoL as the primary endpoint and the study will be conducted in a large number of sites in England and Scotland to ensure the sample size will be recruited in a timely manner. If they decide to proceed with the study they will be invited to the hospital for a screening visit. At this visit, consent will be received and blood will be taken for routine analysis and a sample of ascitic fluid will be taken to ensure there is no underlying infection. If there is this will be treated with oral antibiotics prior to any drain insertion. If the participant is eligible and they are willing to continue they will be randomised to either the Intervention (the LTAD) or standard of care (LVP). The participant will receive a phone call prior to the baseline visit so that the treatment group can be discussed with them and they know what to expect at that visit. At the baseline visit, safety blood will be taken as well as vital signs. At this visit, the questionnaires are completed. There are between three to four questionnaires to be completed by the participant at each visit with a total of 6 visits after the baseline visit. If the participant is randomised to the LTAD arm they will be followed up at home by a community nurse who will visit 2- 3 times a week to drain the ascites. Informal caregivers can be trained to do this if they are willing. Those randomised to the LVP arm will attend the hospital for drainage of the ascites in line with the standard of care. All participants will also receive a fortnightly home visit from the research team for safety monitoring, routine clinical bloods, collection of LTAD drainage data collated by the community nurses and for completion of the questionnaires. In those randomised to LVP, if hospital visits coincide with the fortnightly home visits, the clinical bloods and questionnaire-based assessments can be performed at the hospital. There is also the option for all participants, their informal caregivers if they have one, and healthcare professionals to participate in a qualitative interview. This one-off interview is to gain a deeper understanding of the issues affecting the participants/caregivers/healthcare professionals and to gain a more in-depth understanding of views and perceptions of ascites drainage via the LTAD vs. LVP. The interviews will be conducted at a one-off time point during the 12 weeks they are in the study. There is also an optional research blood sample that if the patient's consent will be taken at the baseline visit and stored for analysis at the end of the study. This sample is purely for research purposes. This study has been supported by extensive Patient & Public Involvement (PPI) and Engagement and leads on from the work undertaken in the feasibility study. The group have helped shape the research methodology, outcome measures and assessment tools and is part of the research team. The service users will provide input throughout the trial. Bespoke training will be provided to the PPI. Previous interventions: Study design This RCT will follow on from the REDUCe feasibility study and will compare the insertion of a palliative tunnelled long-term abdominal drain (LTAD) (Group 1 intervention) to the standard of care (large volume paracentesis (LVP) (Group 2) in the management of refractory ascites due to advanced cirrhosis. This multi-centre, non-blinded parallel-group RCT with up to 3 months of follow-up will be conducted across 35 sites in England and Scotland. We aim to recruit 310 patients. 30 patients, 20 informal caregivers and 20 healthcare professionals will also be invited to give their perceptions/perspectives of LTAD and LVP using qualitative methods. The study will commence recruitment in October/November 2022 and is due to be completed in September 2026 which is the last patient last visit (LPLV). We have built in a 6-month lead-up time to secure HRA approvals and ensure all sites are set up and appropriate training provided. After the LPLV we have time to ensure the dataset is clean and locked for the statisticians to undertake the analysis. These timelines have been reviewed and approved by the funder: NIHR HTA. Participants will be approached by a member of the clinical team and provided with information about the study. The sample size has been calculated using HRQoL as the primary endpoint and the study will be conducted in a large number of sites in England and Scotland to ensure the sample size will be recruited in a timely manner. If they decide to proceed with the study they will be invited to the hospital for a screening visit. At this visit, consent will be received and blood will be taken for routine analysis and a sample of ascitic fluid will be taken to ensure there is no underlying infection. If there is this will be treated with oral antibiotics prior to any drain insertion. If the participant is eligible and they are willing to continue they will be randomised to either the Intervention (the LTAD) or standard of care (LVP). The participant will receive a phone call prior to the baseline visit so that the treatment group can be discussed with them and they know what to expect at that visit. At the baseline visit, safety blood will be taken as well as vital signs. At this visit, the questionnaires are completed. There are between three to four questionnaires to be completed by the participant at each visit with a total of 6 visits after the baseline visit. If the participant is randomised to the LTAD arm they will be followed up at home by a community nurse who will visit 2- 3 times a week to drain the ascites. Informal caregivers can be trained to do this if they are willing. Those randomised to the LVP arm will attend the hospital for drainage of the ascites in line with the standard of care. All participants will also receive a fortnightly home visit from the research team for safety monitoring, routine clinical bloods, collection of LTAD drainage data collated by the community nurses and for completion of the questionnaires. In those randomised to LVP, if hospital visits coincide with the fortnightly home visits, the clinical bloods and questionnaire-based assessments can be performed at the hospital. There is also the option for all participants, their informal caregivers if they have one, and healthcare professionals to participate in a qualitative interview. This one-off interview is to gain a deeper understanding of the issues affecting the participants/caregivers/healthcare professionals and to gain a more in-depth understanding of views and perceptions of ascites drainage via the LTAD vs. LVP. The interviews will be conducted at a one-off time point during the 12 weeks they are in the study. There is also an optional research blood sample that if the patient's consent will be taken at the baseline visit and stored for analysis at the end of the study. This sample is purely for research purposes. This study has been supported by extensive Patient & Public Involvement (PPI) and Engagement and leads on from the work undertaken in the feasibility study. The group have helped shape the research methodology, outcome measures and assessment tools and is part of the research team. The service users will provide input throughout the trial. Bespoke training will be provided to the PPI. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Liver-specific health-related quality of life (HRQoL) measured using the short-form-liver disease quality of life (SFLDQoL) questionnaire at 3 months |
| Secondary outcome measures | 1. Cumulative incidence of peritonitis in the LTAD and LVP groups measured using standard laboratory methods at 12 weeks. Peritonitis defined as ascitic white cell count > 500 cells/mm3, and/or neutrophil count > 250 cells/mm3 and/or a positive ascitic fluid culture. 2. Ascites-related symptoms measured using the Ascites Q questionnaire at baseline and weeks 2, 4, 6, 8, 10 and 12 3. Workload impact on the caregiver assessed using the Caregiver Roles and Responsibilities Scale (CRRC) at baseline and weeks 4, 8 and 12 4.1. Health Resource Utilisation measured using the modified Ambulatory and Home Care Record (AHCR) for community service use at baseline and weeks 4, 8 and 12 4.2. Hospital service use measured using the Hospital Service use in-house designed questionnaire (to be completed by a member of the research team) at the week 12 visit 4.3 Cost-utility measured using the EQ-5D-5L questionnaire to generate adjusted life years (QALYs) at baseline and weeks 2, 4, 6, 8, 10 and 12 |
| Overall study start date | 01/05/2022 |
| Overall study end date | 30/09/2026 |
Eligibility
| Participant type(s) | Patient, Health professional, Carer, Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 310; UK Sample Size: 310 |
| Participant inclusion criteria | Current inclusion criteria as of 04/12/2024: 1. Aged 18 years old and over 2. Refractory ascites due to cirrhosis (with the need for one or more LVP per month), defined as per International Ascites Club criteria (5-6): -Diuretic-resistant ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment (spironolactone 400 mg and furosemide 160 mg) and or Diuretic-intractable ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage 3. Registered with a GP in the community Trusts served by the participating centres. 4. Capacity to give informed consent. _____ Previous participant inclusion criteria as of 01/11/2023: 1. Aged 18 years old and over 2. Refractory ascites due to cirrhosis (with the need for one or more LVP per month), defined as per International Ascites Club criteria (5-6): 3. Diuretic-resistant ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment (spironolactone 400 mg and furosemide 160 mg) and or Diuretic-intractable ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage 4. Registered with a GP in the community Trusts served by the participating centres. _____ Previous participant inclusion criteria: 1. Aged 18 years old and over 2. Refractory ascites (with the need for one or more LVP per month), defined as per International Ascites Club criteria (5-6): 3. Diuretic-resistant ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment (spironolactone 400 mg and furosemide 160 mg) and or Diuretic-intractable ascites: ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic-induced complications that preclude the use of an effective diuretic dosage 4. Registered with a GP in the community Trusts served by the participating centres. |
| Participant exclusion criteria | Current exclusion criteria as of 04/12/2024: 1. Loculated and or chylous ascites 2. Evidence of active infection that in the investigator’s opinion would preclude insertion of LTAD (for example, bacterial peritonitis) – such patients would need to receive appropriate treatment and could then be reconsidered 3. A candidate for liver transplantation and or TIPS 4. Psychosocial issues which in the opinion of the medical team will preclude study participation 5. Pregnancy - all women of childbearing age must have a negative pregnancy test 6. Lacks Capacity to give informed consent _____ Previous exclusion criteria: 1. Loculated and or chylous ascites 2. Evidence of active infection that in the investigator’s opinion would preclude insertion of LTAD (for example, bacterial peritonitis) – such patients would need to receive appropriate treatment and could then be reconsidered 3. A candidate for liver transplantation and or TIPS 4. Psychosocial issues which in the opinion of the medical team will preclude study participation 5. Pregnancy - all women of childbearing age must have a negative pregnancy test |
| Recruitment start date | 01/10/2022 |
| Recruitment end date | 30/06/2026 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Worthing
BN11 2DH
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Derriford
Plymouth
PL6 8DH
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
C Floor, Huntsmnan Building
Herries Road
Sheffield
S5 7AU
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
London
SE5 9RS
United Kingdom
Hull
HU3 2JZ
United Kingdom
Farnworth Bolton
Bolton
BL4 0JR
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Glasgow
G12 0XH
United Kingdom
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Derby
DE22 3NE
United Kingdom
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
Hamilton
ML3 0TA
United Kingdom
Brighton
BN2 5BE
United Kingdom
North Shields
NE29 8NH
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Pontyclun
CF72 8XR
United Kingdom
Waverley Gate
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Whitechapel
London
E1 1BB
United Kingdom
Guildford
GU2 7XX
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Sherriff Hill
Gateshead
NE9 6SX
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Treliske
Truro
TR1 3LJ
United Kingdom
Durham
DH1 5TW
United Kingdom
Sponsor information
University/education
Sussex House
Falmer
Southern Ring Road
Brighton
BN1 9RH
England
United Kingdom
| Phone | +44 (0)1273872748 |
|---|---|
| researchsponsorship@sussex.ac.uk | |
| Website | https://www.sussex.ac.uk/ |
"ROR" |
https://ror.org/00ayhx656 |
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 | 30/09/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Other publication No identifiable personal data will be used when publishing results, only annonymised data. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/12/2024: The following changes were made to the trial record:
1. The inclusion criteria were updated.
2. The exclusion criteria were updated.
3. The study participating centre Great Western Hospitals NHS Foundation Trust was removed and New Cross Hospital Royal Wolverhampton, Gateshead Hospitals NHS Trust, The James Cook University Hospital, Royal Cornwall Hospitals NHS Trust, University Hospital of North Durham were added.
01/11/2023: The following changes have been made:
1. The study setting Community was added.
2. The study types Safety and Efficacy were added.
3. The interventions were changed.
4. The participant inclusion criteria were changed.
5. The participant types Patient, Health professional and Carer were added.
6. The study participating centres St Marys Hospital, University Hospitals Bristol and Weston NHS Foundation Trust, Blackpool Teaching Hospitals NHS Foundation Trust, Cheltenham General Hospital, NHS Tayside, Brighton General Hospital, Royal United Hospitals Bath NHS Foundation Trust, Doncaster Royal Infirmary, James Cook University Hospital and NHS North Tyneside Ccg were removed.
7. Wales was added as a country of recruitment.
8. The ethics approval date was changed from 05/08/2022 to 29/06/2022.
9. The study participating centres Royal Sussex County Hospital, North Tyneside General Hospital, Addenbrookes Hospital, Gloucestershire Royal Hospital, The Royal Glamorgan Hospital, NHS Lothian, The Royal London Hospital and Royal Surrey County Hospital were added.
19/10/2022: Trial website added.
28/07/2022: Trial's existence confirmed by NIHR.
