Clinical trial NCT03847285: Immune Function as Predictor of Infectious Complications and Clinical Outcome in Patients Undergoing Solid Organ Transplantation
Official title: Immune Function as Predictor of Infectious Complications and Clinical Outcome in Patients Undergoing Solid Organ Transplantation: A Prospective Non-interventional Observational Trial
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Transplant
Keywords: Transplant
Infection
rejection
immunology
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2019-02-20
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants must have a planned kidney, heart, lung, liver or pancreas transplant or be on the waiting list for a heart, lung, liver or pancreas-transplantation at 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.

Eligibility criteria: 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

Primary outcomes:
measure: Infection
timeFrame: one year
measure: graft rejection
timeFrame: one year
Secondary outcomes:
measure: combined endpoints at 28 days post transplantation
timeFrame: 28 days
measure: combined endpoints at 90 days post transplantation
timeFrame: 90 days
measure: combined endpoints at 2 years post transplantation
timeFrame: 2 years
measure: combined endpoints at 5 years post transplantation
timeFrame: 5 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Susanne Dam Nielsen, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drabe CH, Sorensen SS, Rasmussen A, Perch M, Gustafsson F, Rezahosseini O, Lundgren JD, Ostrowski SR, Nielsen SD. Immune function as predictor of infectious complications and clinical outcome in patients undergoing solid organ transplantation (the ImmuneMo:SOT study): a prospective non-interventional observational trial. BMC Infect Dis. 2019 Jul 3;19(1):573. doi: 10.1186/s12879-019-4207-9.