Outcome Analysis of Aspirin in Liver Transplantation

Liver Transplant; Complications Clinical Trial

Official title:

Outcome Analysis of Antiplatelet Therapy With Aspirin in Liver Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04327427
• Other study ID #: 2017-01889
• Status: Recruiting
• Start date: October 1, 2019
• Est. completion date: May 31, 2021

Study information

• Verified date: March 2020
• Source: University of Zurich
• Contact: Christian E Oberkofler, MD
• Phone: 0041792961264
• Email: christian.oberkofler[@]usz.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In the experimental setting inhibition of platelet activation was able to reduce immune-mediated necroinflammatory liver disease and consecutively hepatocellular carcinoma development. Therefore, antiplatelet therapy may not only have a preventive effect on hepatic artery patency but also on tumor recurrence.

So far and to the best of our knowledge, no study investigated the effect of antiplatelet therapy on hepatic arterial patency, tumor recurrence and graft survival after primary liver transplantation.

Description:

Outcome Analysis of antiplatelet therapy with Aspirin in Liver Transplantation

BACKGROUND Arterial complications after liver transplantation (LT) are still one of the most serious complications, which might result in liver necrosis, abscess formation, ischemic cholangiopathy, and eventually graft loss. The sequel of these adverse events has a negative impact on graft and patient survival and remains a life-threatening complication with a high mortality and retransplantation rate. Therefore, an uncompromised inflow of the hepatic artery is crucial to avoid any occlusion after LT.

In the literature, the incidence of hepatic artery thrombosis ranges between 2.5 and 10%. So far, the possibility of preventing hepatic artery thrombosis through specific pharmacological prophylaxis with antiplatelet agents (Aspirin) has been poorly investigated, which may be in part due to the impaired coagulative state at the time of transplantation and the early postoperative period. On the other hand, platelets, the chief effectors of vascular homeostasis, have been identified as important players in the pathogenesis of both acute and chronic liver diseases in animal models.

In the experimental setting inhibition of platelet activation was able to reduce immune-mediated necro-inflammatory liver disease and consecutively hepatocellular carcinoma development. Therefore, antiplatelet therapy may not only have a preventive effect on hepatic artery patency but also on tumor recurrence.

So far and to the best of our knowledge, no study investigated the effect of antiplatelet therapy on hepatic arterial patency, tumor recurrence and graft survival after primary liver transplantation.

STUDY OBJECTIVES The primary goal of this study is to conduct a multicentre cohort analysis to investigate whether antiplatelet therapy with Aspirin has an impact on hepatic arterial patency after primary liver transplantation.

Specific aim #1: To evaluate if antiplatelet therapy with Aspirin has a protective effect on arterial patency after primary LT.

Specific aim #2: To identify if antiplatelet therapy with Aspirin has a protective effect on acute cellular rejection.

Specific aim #3: To identify if antiplatelet therapy with Aspirin has protective effect on tumor recurrence (HCC).

Specific aim #4: To investigate whether antiplatelet therapy with Aspirin has a protective effect on graft survival.

STUDY DESIGN This will be a multicentre single cohort study including only cases of deceased donor primary liver transplantation. Primary endpoint is 30-day arterial patency in patients with or without antiplatelet therapy with Aspirin after liver transplantation. Secondary endpoints include postoperative complications, tumor recurrence, graft- and patient survival. The study protocol has received approval by the local ethics committee (2016-01889) as well as published here prior to data collection.

SETTING This multicentre cohort study will include several high-volume centres worldwide. Each participating centre requires a prospective database from that data can be extracted. All consecutive cases of deceased donor liver transplantation requiring from 1st of January 2013 until 31st of December 2015 are included allowing a minimum follow-up time of 24 months. Data collection at Aspirin4olt.org will be prospective, structured, anonymized, and encrypted.

PUBLICATION POLICY For upcoming publications, two authorships of the participating centres will be guaranteed as a group-authorship indexed in PubMed.

INSTITUTIONAL REVIEW POLICY / ETHICAL POLICY Each participating centre is responsible to contact their local ethics committee and receive approval for participation, if applicable. For example, this project is considered as an audit in some countries and thus there is no need for formal approval in the form of a protocol submission.

ELIGIBILITY CRITERIA

Inclusion criteria:

Adult Liver transplantation (age ≥18 years) Deceased donor after brain death (DBD) or deceased donor after circulatory death (DCD) Primary liver transplantation, whole graft Arterial anastomosis: end-to-end, back table reconstruction

Exclusion criteria:

Split liver and living donor liver transplantation Paediatric liver transplantation (recipient age <18 years) Arterial conduits Multivisceral transplantations Retransplantations

ESTIMATED SAMPLE SIZE Each centre should provide at least 30 cases that meet the inclusion criteria to allow adequate event rates for each outcome.

Statistical methods The primary and secondary endpoints will be compared with patient and operation characteristics with univariate analysis. ROC Curve analysis will be performed to dichotomize continuous variables. Multivariable analysis (binary logistic and Cox regression) will be performed to identify independent risk factors. Statistical analysis will be performed using R Studio version 1.0.44 (RStudio, Inc. GNU Affero General Public License v3, Boston, MA, 2016) with the graphical user interface rBiostatistics.com beta version (rBiostatistics.com, London, UK, 2017, GNU License).

Christian E. Oberkofler Philip C. Müller Dimitri A. Raptis Henrik Petrowsky On behalf of the Aspirin4olt.org team Swiss HPB Center, Department of Surgery and Transplantation, University Hospital Zurich, Switzerland

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: May 31, 2021
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult Liver transplantation(age =18 years)

• Deceased donor after brain death (DBD) or deceased donor after circulatory death (DCD)

• Primary liver transplantation, whole graft

• Arterial anastomosis: end-to-end, back table reconstruction

Exclusion Criteria:

• Split liver and living donor liver transplantation

• Paediatric liver transplantation (recipient age <18 years)

• Arterial conduits

• Multivisceral transplantations

• Retransplantations

Related Conditions & MeSH terms

• Liver Transplant; Complications

Intervention

Other:
• Aspirin
Outcome Analysis of Aspirin in liver transplantation

Locations

Country	Name	City	State
Switzerland	Department of Visceral and Transplantation Surgery	Zurich	CH/Zürich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aspirin and arterial patency	We will look, if antiplatelet therapy with Aspirin has a protective effect on arterial patency after primary liver transplantation by looking at postoperative lab values and imaging, if they were perfromed.	2 years
Secondary	Aspirin and cellular rejection	We will analyze patients with and without postoperative cellular rejection and the intake of Aspirin.	2 years
Secondary	Aspirin and tumor recurrence	We will look at post transplant tumor recurrence and if the recurrence does correlate with Aspirin intake.	2 years
Secondary	Aspirin and graft survival	We will look at the postoperative graft survival and devide graft survival in the group of patients who were under Aspirin postoperative with those who did not take Aspirin postoperative; both groups will be then compared.	2 years