Donor Specific HLA Alloantibodies in Liver Transplantation

NCT02784080 | Active Not Recruiting

• 1 other identifier: H-15007823
• Study Type: observational
• Target: 858
• Locations: 4 countries
• Sites: 5

Brief 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.

Conditions

Complication of Transplanted Liver

Keywords

Liver Transplantation; HLA alloantibodies; donor specific antibodies; Mortality; Re-transplantation; Rejection; Acute rejection; Chronic rejection; Biliary complications; Biliary stricture; Arterial thrombosis; Arterial stenosis; Portal vein thrombosis; Fibrosis; Single antigen bead; Cross-match

Outcome Measures

Primary Outcomes (1)

• All-cause mortality or re-transplantation (graft loss)

  Minimum 1 year, accrual to study end

Secondary Outcomes (6)

• 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

• Acute rejection, both cellular and humoral rejection, as defined by Banff classification.

  Minimum 1 year, accrual to study end

• 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

• Fibrosis, defined by METAVIR score.

  Minimum 1 year, accrual to study end

• Vascular complications (hepatic arterial stenosis, hepatic arterial thrombosis, portal vein thrombosis).

  Minimum 1 year, accrual to study end

Study Arms (1)

HLA-alloantibodies exposure

Preformed, persistent, and de novo HLA-alloantibody exposure in the whole cohort.

Other: HLA-alloantibodies exposure

Interventions

HLA-alloantibodies exposure OTHER

Following analyzes will be done: LABScreen® Single Antigen, One Lambda, CA C1qScren™, One Lambda, CA (planned for later study) PE-conjugated IgG3 antibody (planned for later study) LABScreen® Mixed, One Lambda, CA (never analysed in the study)

HLA-alloantibodies exposure

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All liver transplant recipients, both children and adults, in the Scandiatransplant region. The Scandiatransplant is an organ exchange organization that comprise of five centers in the Nordic countries: Norway, Sweden, Finland and Denmark. The five centers cover the need for liver transplantation in approximately 25 million people. From 2010-2015 the following number of transplants were done in Scandiatransplant according to the number of available donors: 323, 352, 353, 365, 388, and 401. Preliminary sample size calculations have estimated inclusion of 1062 adult and 100 pediatric patients during a study period of 3 years. Interim sample size calculations will be done, if necessary the study period will be prolonged. Pediatric patients will be analyzed separately.

You may qualify if:

• Undergo a liver transplanted during the study period.
• Pre-transplant serum sample of minimum 4 ml (relevant for pediatric patients)
• Informed consent is given.

You may not qualify if:

• Withdrawal of informed consent.
• Blinding broken in a non-protocoled manner the patient will be excluded.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Sahlgrenska University Hospital: collaborator
• Karolinska Institutet: collaborator
• Helsinki University Central Hospital: collaborator
• Oslo University Hospital: collaborator

Study Sites (5)

Department of Surgical Gastroenterology and Transplantation, Rigshospitalet - Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Transplantation and Liver Surgery Clinic, Helsinki University Hospital

Helsinki, PL 372, 00029 HUS, Finland

Location

Department of Transplantation Medicine, Oslo University Hospital

Oslo, 0424, Norway

Location

Surgery Department, Transplantation and Liver Surgery Unit, Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Division of Transplantation Surgery, Karolinska Institutet

Stockholm, 14186, Sweden

Location

Related 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.

  PMID: 24373168 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Recipient samples, pre-transplant, at discharge or day 14 (±4 days, changed to discharge), 3 months (±3 weeks), 1 year (±1 month), and at liver biopsy * 1 Plasma, EDTA-glass (9 ml), redistributed 4 aliquots * 2 Serum, clot activator (9 ml + 4 ml), redistributed 8 aliquots * Liver biopsy sample: Formalin fixed paraffin-embeded

MeSH Terms

Conditions

Rejection, Psychology; Fibrosis

Condition Hierarchy (Ancestors)

Social Behavior; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Allan Rasmussen, MD

  Department of Surgical Gastroenterology and Transplantation, Rigshospitalet - Copenhagen University Hospital, Denmark

  STUDY CHAIR

• Andreas A Rostved, MD

  Department of Surgical Gastroenterology and Transplantation, Rigshospitalet - Copenhagen University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

• Helle Bruunsgaard, MD, DMSc

  Department of Clinical Immunology, Centre of Diagnostic Investigation, Rigshospitalet - Copenhagen University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 26, 2016
• Study Start: August 15, 2015
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

FI (1); DK (1); NO (1); SE (2)