Donor Specific HLA Alloantibodies in Liver Transplantation

Complication of Transplanted Liver Clinical Trial

Official title:

Donor Specific HLA Alloantibodies in Liver Transplantation: a Prospective Blinded Multicenter Prognostic Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02784080
• Other study ID #: H-15007823
• Status: Recruiting
• Start date: August 2015
• Est. completion date: September 2021

Study information

• Verified date: February 2020
• Source: Rigshospitalet, Denmark
• Contact: Andreas A Rostved, MD
• Phone: +4521787364
• Email: andreas.arendtsen.rostved[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim is to evaluate the impact of donor specific HLA alloantibodies (DSA) on all-cause mortality and re-transplantation, early allograft dysfunction, acute and chronic rejection, fibrosis, vascular, and biliary complications. Furthermore, all biopsies will be C4d stained. The hypothesizes is that donor specific HLA alloantibodies facilitate an immune mediated damage to the liver allograft that impairs function and lead to various complications.

The investigators will do a prospective blinded multicenter cohort study in the Scandiatransplant organ sharing organization region.

Both preformed, persistent, and de novo donor specific HLA alloantibodies will studied. Blood samples will be taken immediately prior to transplantation, and 14 days, 3 months, and 1 year after transplantation. All liver biopsies performed during the study period will be evaluated for a humoral component and blood samples will be obtained prior to liver biopsies to investigate the presence of DSA.

Investigations will be fully blinded for the treatment responsible doctors.

Description:

The outcome after liver transplantation has improved drastically over time, but this development has stagnated in recent years to a graft failure rate of 9-15 % within the first year and approximately 20-30 % at 5 years [1]. The primary goal is to improve the outcome after liver transplantation.

The impact of donor specific antibodies (DSA) on all-cause mortality and re-transplantation, early allograft dysfunction, acute and chronic rejection, vascular and biliary complications and fibrosis will be investigated.

Objectives:

1. The primary objective is to investigate if DSA both pre-formed, persistent, and de novo affect survival and allograft loss. For patients diagnosed with HLA antibodies a standard Luminex single antigen IgG analysis, a Luminex C1q and an IgG3 single antigen assay will be performed.

2. The secondary objective is to investigate if donor specific antibodies, both pre-formed, persistent, and de novo increase the risk of early allograft dysfunction, acute and chronic rejection, fibrosis, de novo autoimmune hepatitis (pediatric patients only), vascular and biliary complications. All liver biopsies will be stained by C4d and a DSA analysis will be undertaken.

3. Continuous measurements will be used to establish the kinetics of both preformed og de novo DSA after liver transplantation.

Pediatric patients will be analyzed separately.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1162
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Undergo a liver transplanted during the study period.

• Pre-transplant serum sample of minimum 4 ml (relevant for pediatric patients)

• Informed consent is given.

Exclusion Criteria:

• Withdrawal of informed consent.

• Blinding broken in a non-protocoled manner the patient will be excluded.

Related Conditions & MeSH terms

• Complication of Transplanted Liver

Intervention

Other:
• HLA-alloantibodies exposure
Following analyzes will be done: LABScreen® Mixed, One Lambda, CA LABScreen® Single Antigen, One Lambda, CA C1qScren™, One Lambda, CA PE-conjugated IgG3 antibody

Locations

Country	Name	City	State
Denmark	Department of Surgical Gastroenterology and Transplantation, Rigshospitalet - Copenhagen University Hospital	Copenhagen
Finland	Transplantation and Liver Surgery Clinic, Helsinki University Hospital	Helsinki
Norway	Department of Transplantation Medicine, Oslo University Hospital	Oslo
Sweden	Surgery Department, Transplantation and Liver Surgery Unit, Sahlgrenska University Hospital	Göteborg
Sweden	Division of Transplantation Surgery, Karolinska Institutet	Stockholm

Sponsors (5)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Helsinki University Central Hospital, Karolinska Institutet, Oslo University Hospital, Sahlgrenska University Hospital, Sweden

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

References & Publications (1)

Kim WR, Smith JM, Skeans MA, Schladt DP, Schnitzler MA, Edwards EB, Harper AM, Wainright JL, Snyder JJ, Israni AK, Kasiske BL. OPTN/SRTR 2012 Annual Data Report: liver. Am J Transplant. 2014 Jan;14 Suppl 1:69-96. doi: 10.1111/ajt.12581. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality or re-transplantation (graft loss)		Minimum 1 year, accrual to study end
Secondary	Early allograft dysfunction are defined as total bilirubin >10 mg/dl or INR >1.6 at day 7 after liver transplantation or ALT >2000 IU/L within the first 7 days after liver transplantation.		7 days after transplantation
Secondary	Acute rejection, both cellular and humoral rejection, as defined by Banff classification.		Minimum 1 year, accrual to study end
Secondary	Chronic rejection, as defined by Banff classification, and as proposed by O'leary et al "Proposed Diagnostic Criteria for Chronic Antibody-Mediated Rejection in Liver Allografts".		Minimum 1 year, accrual to study end
Secondary	Fibrosis, defined by METAVIR score.		Minimum 1 year, accrual to study end
Secondary	Vascular complications (hepatic arterial stenosis, hepatic arterial thrombosis, portal vein thrombosis).		Minimum 1 year, accrual to study end
Secondary	Biliary complications (biliary leakage, anastomotic biliary stricture, non-anastomotic biliary stricture, liver abscess, cholangitis, other).	Anastomotic strictures and non-anastomotic strictures will be investigated as a combined and solitary outcome.	Minimum 1 year, accrual to study end