Immune Function as Predictor of Infectious Complications and Clinical Outcome in Patients Undergoing Solid Organ Transplantation

Active, not recruiting

• Conditions: Transplant

• Registration Number: NCT03847285
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

At Rigshospitalet, Denmark, we will examine the immune function of solid organ transplant recipients before and at several timepoints after transplantation as well as the clinical outcome, especially the risk of infections complications and graft rejections.

The immune function will be assessed with a complete immunological profiling consisting of immune phenotype (flow cytometry), immune function (TruCulture®) and circulating biomarkers.

The study aims to generate prediction models of patients at excess risk of poor clinical outcome, with the ultimate intent to propose personalized immunosuppressive regimes to be tested in future randomized clinical trials.

Detailed Description

Background: Solid organ transplantation (SOT) is an increasingly used life-saving treatment for end-stage organ failure. Organ rejection and infections are the main complication to SOT and the balance of immunosuppression is of major importance to prevent these complications. However, to date the only mode to monitor treatment is by assessing drug concentrations, which has low correlation with the clinical outcome and does not represent the net state of immunosuppression.

Methods: Prospectively the investigators plan to enroll 600 adult patients on the waiting list for SOT or with a planned transplantation at Rigshospitalet, Denmark. Prior to transplantation and on different time points up to two years post-transplantation we will perform a complete immunological profile. This profile will consist of classical descriptive immune phenotyping (flowcytometry), circulating biomarkers and the functional assay TruCulture®. In TruCulture® whole blood is stimulated with stimulants imitating bacterial, viral and fungal infections, where after a panel of selected cytokines is quantified.

Clinical data from electronic health records will be obtained retrospectively from the PERSIMUNE data repository. These data are generated as part of routine care and include vital signs, biochemistry-, microbiological-, pathological-results as well as data about medication, demographics, diagnoses, hospital contacts, surgical procedures and mortality.

Discussion: This will be the first large scale study to determine several aspects of immune function and perform a complete immunological profiling in SOT recipients. It is expected that this new knowledge will provide information to generate prediction models identifying patients at increased risk of infection and/or rejection. If the study is successful, the investigators will subsequently use the generated prediction models to propose personalized immunosuppressive regimens to be tested in future randomized controlled trials.

Study Timeline

• Study Start: 2018-04-01
• Study First Submitted: 2019-02-06
• Study First Submitted QC: 2019-02-19
• Study First Posted: 2019-02-20
• Primary Completion: 2022-01-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-10
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

• To be eligible for the study the participant must be a minimum of 18 years of age, participate in the PERSIMUNE biobank, have a planned kidney, heart, lung, liver or pancreas transplant or be on the waiting list for a heart, lung, liver or pancreas transplant and be able to sufficiently understand oral and written study information in Danish or English to provide an informed consent. Study participation is strictly voluntary

Exclusion Criteria

• not meeting inclusion criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Infection	one year	Infections (viral, bacterial or fungal) within 1 year after the transplantation
graft rejection	one year	Graft rejection within 1 year after the transplantation. Rejections will be defined by pathologist and clinician.

Secondary Outcome Measures

Name	Time	Method
combined endpoints at 2 years post transplantation	2 years	Combined endpoint of infections (viral, bacterial or fungal) or graft rejection within 2 years
combined endpoints at 90 days post transplantation	90 days	Combined endpoint of infections (viral, bacterial or fungal) or graft rejection within 90 days
combined endpoints at 5 years post transplantation	5 years	Combined endpoint of infections (viral, bacterial or fungal) or graft rejection within 5 years
combined endpoints at 28 days post transplantation	28 days	Combined endpoint of infections (viral, bacterial or fungal) or graft rejection within 28 days

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark