Validation of a Risk Score Opportunistic Infections Development in Kidney Transplant Patients (SIMPLICITY)

• ClinicalTrials.gov Identifier: NCT03083756
• Recruitment Status: Completed
• First Posted: March 20, 2017
• Last Update Posted: March 20, 2017
• Sponsor: Sociedad Española de Trasplante
• Collaborator: Roche Farma, S.A
• Information provided by (Responsible Party): Sociedad Española de Trasplante

Study Description

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).

Condition or disease
Opportunistic Infections

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 577 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Prospective Observational Study for the Validation of a Risk Score Opportunistic Infections Development in Kidney Transplant Patients
• Study Start Date: August 2014
• Actual Primary Completion Date: February 15, 2017
• Actual Study Completion Date: February 15, 2017

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at month of transplantation). [ Time Frame: 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)
2. To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at six months of transplantation. [ Time Frame: 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).

Secondary Outcome Measures :

1. Correlation of IgG and infectious complications [ Time Frame: Up to 12 moths from transplant ]
   Correlation of IgG and the incidence of infectious complications increased.
2. Correlation of C3 and infectious complications [ Time Frame: Up to 12 moths from transplant ]
   Correlation of C3 and the incidence of infectious complications increased.
3. Correlation of count lymphocyte T CD3+ in Peripheral blood and infectious complications [ Time Frame: Up to 12 moths from transplant ]
   Correlation count of lymphocyte subpopulations CD3+ and the incidence of infectious complications increased.
4. Correlation of count lymphocyte T CD8+ in Peripheral blood and infectious complications [ Time Frame: Up to 12 moths from transplant ]
   Correlation count of lymphocyte subpopulations CD8+ and the incidence of infectious complications increased.
5. Acute rejection with histologic confirmation by conventional criteria [ Time Frame: Up to 12 moths from transplant ]
   Number of patients who have had at least one acute biopsy-proven rejection throughout the study.
6. Graft loss with or without retransplantation. [ Time Frame: Up to 12 moths from transplant ]
   Number of patients who have lost the graft throughout the study.
7. Mortality infectious cause [ Time Frame: Up to 12 moths from transplant ]
   Number of dead patients and whose cause of death is Infection.
8. Mortality otherwise. [ Time Frame: 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).
9. CMV infection/Disease [ Time Frame: 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.
10. CMV viremia [ Time Frame: 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).
11. To analyze the influence of low lymphocyte count in the increase of the rate of major infectious complications. [ Time Frame: Up to 12 moths from transplant ]
    Low lymphocyte count, defined as lymphocytes <1500 cells/mcl and the rate of major infectious complications
12. To analyze the influence of CMV serology in the increase of the rate of major infectious complications. [ Time Frame: 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
13. To analyze the influence of Historical PRA (Panel Reactive Antibody) in the increase of the rate of major infectious complications [ Time Frame: Up to 12 moths from transplant ]
    Historical PRA (%) and the rate of major infectious complications
14. To analyze whether viremia has any impact on the occurrence of other opportunistic diseases [ Time Frame: Up to 12 moths from transplant ]
    Presence of major post-transplant infectious complication and the occurrence of other opportunistic diseases.
15. To analyze whether CMV disease has any impact on the occurrence of other opportunistic diseases. [ Time Frame: Up to 12 moths from transplant ]
    Presence of CMV disease and the occurrence of other opportunistic diseases.
16. To analyze the role of Anticipated treatment and the influence in the appearance of infection or disease by CMV. [ Time Frame: Up to 12 moths from transplant ]
    Indication of Anticipated treatment and appearance of infection or disease by CMV.
17. To analyze the role of Antiviral prophylaxis and the influence in the appearance of infection or disease by CMV. [ Time Frame: Up to 12 moths from transplant ]
    Indication of Antiviral prophylaxis appearance of infection or disease by CMV.
18. 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. [ Time Frame: 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.
19. 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. [ Time Frame: 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.
20. 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. [ Time Frame: 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.
21. 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. [ Time Frame: 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.
22. 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. [ Time Frame: 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.
23. 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. [ Time Frame: 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.
24. 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. [ Time Frame: 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.
25. 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. [ Time Frame: 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.
26. 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. [ Time Frame: 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.
27. 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. [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Renal transplant patients

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

Spain

Hospital Marqués de Valdecilla

Santander, Cantabria, Spain, 39008

Hospital Son Espases

Palma de Mallorca, Islas Baleares, Spain, 07120

Hospital Dr. Negrín

Las Palmas de Gran Canaria, La Palmas, Spain, 35010

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain, 28222

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain, 30120

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain, 15006

Hospital del Mar

Barcelona, Spain, 08003

Hospital Vall d´Hebrón

Barcelona, Spain, 08035

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Hospital Ramón y Cajal

Madrid, Spain, 28034

Hospital Universitario 12 Octubre

Madrid, Spain, 28041

Hospital Carlos Haya

Málaga, Spain, 29010

Hospital Virgen de la Salud

Toledo, Spain, 45071

Hospital Universitario Doctor Peset

Valencia, Spain, 46017

Hospital Miguel Servet

Zaragoza, Spain, 50009

Sponsors and Collaborators

Sociedad Española de Trasplante

Roche Farma, S.A

Investigators

• Study Chair: José María Aguado, MD; Hospital Universitario 12 de Octubre
• Study Chair: Daniel Serón, MD; Hospital Universitario Vall d´Hebrón
• Study Chair: Ángel Alonso, MD; Hospital Universitario de A Coruña
• Principal Investigator: Domingo Hernández Marrero, MD; Hospital Carlos Haya
• Principal Investigator: Álex Gutiérrez Dalmau, MD; Hospital Miguel Servet
• Principal Investigator: Roberto Gallego, MD; Hospital Dr. Negrín
• Principal Investigator: Juan Carlos Ruiz, MD; Hospital Marqués de Valdecilla
• Principal Investigator: Frederic Cofàn, MD; Hospital Clinic of Barcelona
• Principal Investigator: José M Cruzado, MD; Hospital Universitari de Bellvitge
• Principal Investigator: Daniel Serón, MD; Hospital Universitario Vall d´Hebrón
• Principal Investigator: María José Pérez Sáez, MD; Hospital del Mar
• Principal Investigator: Miguel Angel Muñoz Cepeda, MD; Hospital Virgen de la Salud
• Principal Investigator: Ángel Alonso, MD; Hospital Universitario de A Coruña
• Principal Investigator: Gonzalo Gómez, MD; Hospital Son Espases
• Principal Investigator: Amado Andrés, MD; Hospital Universitario 12 de Octubre
• Principal Investigator: José Mª Portolés, MD; Hospital Universitario Puerta de Hierro Majadahonda
• Principal Investigator: Roberto Marcén, MD; Hospital Universitario Ramon y Cajal
• Principal Investigator: Luisa Jimeno Garcia, MD; Hospital Virgen de la Arrixaca
• Principal Investigator: Luis M Pallardó Mateu, MD; Hospital Dr. Peset

More Information

• Responsible Party: Sociedad Española de Trasplante
• ClinicalTrials.gov Identifier: NCT03083756
• Other Study ID Numbers: SET-INF-2014-01
• First Posted: March 20, 2017
• Last Update Posted: March 20, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; Opportunistic Infections; Disease Attributes; Pathologic Processes