Validation of a Risk Score Opportunistic Infections Development in Kidney Transplant Patients
- Conditions
- Opportunistic Infections
- Registration Number
- NCT03083756
- Lead Sponsor
- Sociedad Española de Trasplante
- Brief Summary
This study validate the usefulness of SIMPLICITY score to characterize the immune status of the kidney transplant receiver at two points along its course (the one and six months after transplantation), by determination in peripheral blood of various parameters related to cellular immunity (count subpopulations of CD3+ (cluster of differentiation 3), CD4+ (cluster of differentiation 4) and CD8+( cluster of differentiation 8)), humoral immunity (immunoglobulins count) and innate (complement).
- Detailed Description
The monitoring of various parameters related to cellular and humoral immunity (lymphocytes, immunoglobulins and complement) through a score (SIMPLICITY) (8) would allow the identification of renal transplant recipients at high risk for post-transplant infection. Prolonged or prolonged use of CMV (Cytomegalovirus) prophylaxis may modify this risk.
The SIMPLICITY score (Seeking for Immune Status based on Peripheral Blood Lymphocytes, Immunoglobulins and Complement Activity) is a practical score based on the monitoring of readily available immunological parameters to assess the risk of infection after RT (Renal transplant). In order to perform this score, the total lymphocyte counts and peripheral blood lymphocyte subpopulations (PBLSs), serum immunoglobulin levels (IgG, IgA (Immunoglobulin A) and IgM) and serum complement levels (C3 and C4) at baseline were investigated, at one month and 6 months after transplantation.
The validation of this new score would allow to have a weapon that would lead to reduce to the maximum the pharmacological immunosuppression and to use strict prophylactic measures in these patients.
The results of the present study may provide insight into clinically and scientifically relevant aspects of infection in the recipient of an RT undergoing immunosuppressive therapy:
From the point of view of assistance, if the hypothesis of the study were confirmed, the possibility of elaborating specific strategies of prophylaxis and early treatment (antibiotic, antifungal or antiviral), adjusted to the risk of the recipient to present some infectious event during its evolution post transplantation according to the SIMPLICITY score.
Likewise, it could lay the foundations for the design of individualized immunosuppression guidelines, in which the risk of infectious complications could be evaluated jointly with that of graft rejection. And all this based on simple immunological parameters, of economic determination and accessible for most of the centers of our environment, circumstance that would favor its immediate application in the usual clinical practice.
Given that the literature on this line of research is scarce, and the hypothesis we intend to demonstrate is novel and conceptually attractive, the results of this study will be able to be published in journals with a high impact index in the field of immunology and Management of infectious complications in the RT.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 577
- Renal transplant patients whose variables can be properly monitored throughout the first year post-transplant.
- Older than 18 years.
- Patients who have signed the informed consent form.
- Infection with the human immunodeficiency virus (HIV).
- Patient who dies during the first month after transplant.
- Pre-transplant diagnosis of primary immunodeficiency (eg. Common variable immunodeficiency, idiopathic CD4 lymphopenia, etc)
- Patient is participating in another clinical trial with a molecule under investigation.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at six months of transplantation. At 6 months from transplant To validate the SIMPLICITY will be scored from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months).
To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at month of transplantation). At 1 month from transplant To validate the SIMPLICITY will be scored from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)
- Secondary Outcome Measures
Name Time Method Correlation of IgG and infectious complications Up to 12 moths from transplant Correlation of IgG and the incidence of infectious complications increased.
Correlation of C3 and infectious complications Up to 12 moths from transplant Correlation of C3 and the incidence of infectious complications increased.
Correlation of count lymphocyte T CD3+ in Peripheral blood and infectious complications Up to 12 moths from transplant Correlation count of lymphocyte subpopulations CD3+ and the incidence of infectious complications increased.
Correlation of count lymphocyte T CD8+ in Peripheral blood and infectious complications Up to 12 moths from transplant Correlation count of lymphocyte subpopulations CD8+ and the incidence of infectious complications increased.
Acute rejection with histologic confirmation by conventional criteria Up to 12 moths from transplant Number of patients who have had at least one acute biopsy-proven rejection throughout the study.
Mortality infectious cause Up to 12 moths from transplant Number of dead patients and whose cause of death is Infection.
Mortality otherwise. Up to 12 moths from transplant Number of dead patients whose cause of death has indicated a different cause to Infection (ie the reason for death was due to ischemic heart disease, or by another cardiovascular complication, or by neoplastic disease or by others).
To analyze whether viremia has any impact on the occurrence of other opportunistic diseases Up to 12 moths from transplant Presence of major post-transplant infectious complication and the occurrence of other opportunistic diseases.
To analyze the role of Antiviral prophylaxis and the influence in the appearance of infection or disease by CMV. Up to 12 moths from transplant Indication of Antiviral prophylaxis appearance of infection or disease by CMV.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 6 months of transplantation on overall survival throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 6 months of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months)) and overall survival throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 6 months of transplantation on vascular disease throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 6 months of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months)) and vascular disease throughout the first year of evolution.
Graft loss with or without retransplantation. Up to 12 moths from transplant Number of patients who have lost the graft throughout the study.
To analyze the influence of CMV serology in the increase of the rate of major infectious complications. Up to 12 moths from transplant CMV receptor serology vs. donor CMV Serology (ie, a new categorical variable will be constructed combining donor and recipient serology: D+/R+, D-/R +,D-/R-, D+/R-) and the rate of major infectious complications
To analyze the influence of Historical PRA (Panel Reactive Antibody) in the increase of the rate of major infectious complications Up to 12 moths from transplant Historical PRA (%) and the rate of major infectious complications
To analyze whether CMV disease has any impact on the occurrence of other opportunistic diseases. Up to 12 moths from transplant Presence of CMV disease and the occurrence of other opportunistic diseases.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 1 month of transplantation on graft survival throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 1 month of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)) and graft survival throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 1 month of transplantation on the incidence of acute rejection throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 1 month of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)) and the incidence of acute rejection throughout the first year of evolution.
CMV infection/Disease Up to 12 moths from transplant Percentage of patients presenting at least one CMV disease throughout the study, from the transplant and number of CMV diseases per patient.
CMV viremia Up to 12 moths from transplant Number of patients who had CMV positive viremia (either PCR (Polymerase Chain Reaction) or antigenemia) at least during one visit (No. of copies\>0 IU/mL in PCR or\>100,000/cell in Antigenemia).
To analyze the influence of low lymphocyte count in the increase of the rate of major infectious complications. Up to 12 moths from transplant Low lymphocyte count, defined as lymphocytes \<1500 cells/mcl and the rate of major infectious complications
To analyze the role of Anticipated treatment and the influence in the appearance of infection or disease by CMV. Up to 12 moths from transplant Indication of Anticipated treatment and appearance of infection or disease by CMV.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 1 month of transplantation on diabetes throughout the first year of evolution throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 1 month of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)) and diabetes throughout the first year of evolution throughout the first.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 6 months of transplantation on graft survival throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 6 months of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months)) and graft survival throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 6 months of transplantation on the incidence of acute rejection throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 6 months of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months)) and the incidence of acute rejection throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 1 month of transplantation on vascular disease throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 1 month of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)) and vascular disease throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 1 month of transplantation on overall survival throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 1 month of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD8+ (\<0.200x103/MicroL at month 1)) and overall survival throughout the first year of evolution.
To analyze the influence of the renal transplant recipient's SIMPLICITY Score at 6 months of transplantation on diabetes throughout the first year of evolution throughout the first year of evolution. Up to 12 moths from transplant SIMPLICITY Score at 6 months of transplantation (from 0 to 3, assigning one point to each of the following parameters: IgG hypogammaglobulinemia (\<700 mg/ dL) , C3 hypocomplementemia (\<83 mg/dL) and low counts in Peripheral blood of lymphocyte T CD3+ (\<0.500x103 MicroL at 6 months)) and diabetes throughout the first year of evolution throughout the first.
Trial Locations
- Locations (15)
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Dr. Negrín
🇪🇸Las Palmas de Gran Canaria, La Palmas, Spain
Hospital Universitario 12 Octubre
🇪🇸Madrid, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital Virgen de la Salud
🇪🇸Toledo, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Spain
Hospital Carlos Haya
🇪🇸Málaga, Spain
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Vall d´Hebrón
🇪🇸Barcelona, Spain