A trial of a clot-busting treatment in livers before transplantation
| ISRCTN | ISRCTN15211703 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15211703 |
| IRAS number | 297403 |
| Secondary identifying numbers | IRAS 297403 |
- Submission date
- 05/06/2021
- Registration date
- 03/08/2021
- Last edited
- 15/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Transplanted livers are susceptible to develop scarring in the bile ducts due to blockage of the blood supply to the wall of the bile duct around the time of transplant. These blocks are thought to be caused by blood clots developing as the liver recovers from a period of storage outside the body. The walls of bile ducts that have had their blood supply blocked heal by scarring, causing narrowed areas in the duct (strictures). Livers from donors donating after circulatory death, as opposed to brain dead donors, are particularly prone to develop this problem.
This study will place a liver on a perfusion machine outside the body and use a clot busting treatment that has been shown to work in non-transplanted livers to break down any clots that form before the liver is transplanted. This clot busting treatment cannot be given after a transplant because of the risk of bleeding in the recipient, something that is not a problem on a perfusion machine.
This study will look at the incidence of bile duct scarring, but the main aim is verify the safety of this approach looking at the incidence of bleeding post-transplant intraoperatively
Who can participate?
Patients having a liver transplant in the participating centres
What does the study involve?
The liver is treated with a clot-busting treatment while it is being perfused on a machine before transplantation
What are the possible benefits and risks of participating?
Benefits: There may be a reduced chance of developing bile duct strictures
Risks: Bleeding post-transplant
Where is the study being run from?
Cambridge University (UK)
When is the study starting and how long is it expected to run for?
June 2021 to December 2024
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Professor Watson, cjew2@cam.ac.uk
Contact information
Scientific
Dept of Surgery, Box 210
Addenbrookes Hospital
Cambridge
CB2 2QQ
United Kingdom
 ORCID ID |
0000-0002-0590-4901 |
|---|---|
| Phone | +44 (0)12232216108 |
| cjew2@cam.ac.uk |
Study information
| Study design | Interventional open label safety and feasibility study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A pilot study of thrombolysis during machine perfusion of circulatory death donor livers to prevent biliary strictures |
| Study objectives | Thrombolytic treatment to livers undergoing machine perfusion reduces cholangiopathy |
| Ethics approval(s) | Approved 16/12/2021, East of England - Cambridge East Research Ethics Committee (Currently being held remotely via Teleconference/ZOOM, The Fulbourn Centre, Home End, Fulbourn, Cambridgeshire, CB21 5BS; +44 (0)207 104 8102, +44 (0)207 104 8102, +44 (0)207 104 8134; cambridgeeast.rec@hra.nhs.uk), ref: 21/EE/0237 |
| Health condition(s) or problem(s) studied | Liver transplantation |
| Intervention | Livers from donors dying following circulatory arrest (DCD donors) undergoing normothermic perfusion will receive a bolus of 10 mg alteplase and 50 ml fresh frozen plasma at the start of perfusion, followed by an infusion of 40 ml alteplase and 200 ml fresh frozen plasma over the next 80 min. A minimum of 100 min perfusion will follow before the liver can be considered for transplantation. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Alteplase |
| Primary outcome measure | Post reperfusion intra-operative blood loss. These data will be obtained from the anaesthetic records and are recored realtime on the electronic patient record |
| Secondary outcome measures | 1. Total and post reperfusion intra-operative blood transfusion and blood loss measured using recorded values on electronic anaesthetic record 2. Proportion of liver perfusions resulting in a transplant measured using aptient records at the end of the study 3. Incidence of symptomatic anastomotic and non-anastomotic strictures at 6 months post-transplant determined at cholangiography; symptomatic meaning associated with raised bilirubin or ALP or cholangitis. 4. Incidence of any anastomotic or non-anastomotic stricture excluding those related to hepatic artery thrombosis determined at cholangiography 5. Incidence of “clinically relevant” non-anastomotic strictures, using the van Rijn definition (associated with raised bilirubin or ALP or cholangitis.) at 6 months 6. Incidence of post reperfusion syndrome: 30% fall in systolic BP lasting at least a minute in the first 5 minutes post reperfusion in the recipient or the need for adrenaline or doubling of noradenaline to support the circulation 7. Early allograft function (Olthoff criteria and model for early allograft function score) at 7 days 8. Incidence of hepatic artery thrombosis in the first 6 months post transplant: determined by CT or angiography 9. Incidence of acute kidney injury (RIFLE criteria) (increase in recipient serum creatinine on days 1 to 7 post transplant compared to the baseline creatinine |
| Overall study start date | 05/06/2021 |
| Completion date | 29/04/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 participants |
| Total final enrolment | 80 |
| Key inclusion criteria | 1. Aged ≥18 years 2. Patient requiring a liver transplant under the care of the participating hospitals |
| Key exclusion criteria | 1. Inability to give consent 2. Recipient of a brain dead donor liver |
| Date of first enrolment | 01/08/2021 |
| Date of final enrolment | 01/12/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
London
NW3 2QG
United Kingdom
Sponsor information
Hospital/treatment centre
R&D Department
Cambridge
CB2 2QQ
England
United Kingdom
| Phone | +44 (0)1223 348468 |
|---|---|
| research@addenbrookes.nhs.uk | |
| Website | https://www.cuh.nhs.uk/ |
"ROR" |
https://ror.org/04v54gj93 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/03/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in specialist peer-reviewed journal. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 03/08/2021 | 09/09/2021 | No | No |
| Protocol file | version 3.2 | 07/05/2022 | 15/06/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 5.1 | 07/02/2023 | 31/07/2023 | No | No |
Additional files
Editorial Notes
15/01/2025: The following changes were made:
1. The overall study end date was changed from 01/06/2023 to 01/12/2024.
2. The total final enrolment was added.
3. The recruitment end date was changed from 01/12/2024 to 29/04/2024.
4. The intention to publish date was changed from 01/01/2024 to 01/03/2025.
31/07/2023: The following changes have been made:
1. Protocol file uploaded.
2. The trial phase has been added.
3. The recruitment end date has been changed from 01/06/2022 to 01/12/2024.
15/06/2022: The following changes have been made:
1. The ethics approval has been updated.
2. The secondary study design has been changed from 'Non-randomised study' to 'Randomised controlled trial'.
3. The overall trial end date has been changed from 06/06/2022 to 01/06/2023 and the plain English summary updated accordingly.
4. The total target enrolment has been changed from 20 to 60.
5. The intention to publish date has been changed from 01/01/2023 to 01/01/2024.
6. An updated protocol has been uploaded.
09/09/2021: The following changes have been made:
1. The protocol (not peer reviewed) has been uploaded as an additional file.
2. The ethics approval has been added.
07/09/2021: Internal review.
03/08/2021: Trial's existence confirmed by Cambridge South REC.
