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

Prospective Observational Study for the Validation of a Risk Score Opportunistic Infections Development in Kidney Transplant Patients

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).

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 577

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall D´Hebron
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre
  • Málaga, Spain, 29010
    • Hospital Carlos Haya
  • Toledo, Spain, 45071
    • Hospital Virgen de la Salud
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
  • Zaragoza, Spain, 50009
    • Hospital Miguel Servet
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marques de Valdecilla
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07120
      • Hospital Son Espases
  • La Palmas
    • Las Palmas de Gran Canaria, La Palmas, Spain, 35010
      • Hospital Dr. Negrín
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de la Arrixaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Renal transplant patients

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at month of transplantation).	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)	At 1 month from transplant
To validate SIMPLICITY Score to characterize the immunological situation of the RT recipient at six months of transplantation.	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).	At 6 months from transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of IgG and infectious complications	Correlation of IgG and the incidence of infectious complications increased.	Up to 12 moths from transplant
Correlation of C3 and infectious complications	Correlation of C3 and the incidence of infectious complications increased.	Up to 12 moths from transplant
Correlation of count lymphocyte T CD3+ in Peripheral blood and infectious complications	Correlation count of lymphocyte subpopulations CD3+ and the incidence of infectious complications increased.	Up to 12 moths from transplant
Correlation of count lymphocyte T CD8+ in Peripheral blood and infectious complications	Correlation count of lymphocyte subpopulations CD8+ and the incidence of infectious complications increased.	Up to 12 moths from transplant
Acute rejection with histologic confirmation by conventional criteria	Number of patients who have had at least one acute biopsy-proven rejection throughout the study.	Up to 12 moths from transplant
Graft loss with or without retransplantation.	Number of patients who have lost the graft throughout the study.	Up to 12 moths from transplant
Mortality infectious cause	Number of dead patients and whose cause of death is Infection.	Up to 12 moths from transplant
Mortality otherwise.	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).	Up to 12 moths from transplant
CMV infection/Disease	Percentage of patients presenting at least one CMV disease throughout the study, from the transplant and number of CMV diseases per patient.	Up to 12 moths from transplant
CMV viremia	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).	Up to 12 moths from transplant
To analyze the influence of low lymphocyte count in the increase of the rate of major infectious complications.	Low lymphocyte count, defined as lymphocytes <1500 cells/mcl and the rate of major infectious complications	Up to 12 moths from transplant
To analyze the influence of CMV serology in the increase of the rate of major infectious complications.	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	Up to 12 moths from transplant
To analyze the influence of Historical PRA (Panel Reactive Antibody) in the increase of the rate of major infectious complications	Historical PRA (%) and the rate of major infectious complications	Up to 12 moths from transplant
To analyze whether viremia has any impact on the occurrence of other opportunistic diseases	Presence of major post-transplant infectious complication and the occurrence of other opportunistic diseases.	Up to 12 moths from transplant
To analyze whether CMV disease has any impact on the occurrence of other opportunistic diseases.	Presence of CMV disease and the occurrence of other opportunistic diseases.	Up to 12 moths from transplant
To analyze the role of Anticipated treatment and the influence in the appearance of infection or disease by CMV.	Indication of Anticipated treatment and appearance of infection or disease by CMV.	Up to 12 moths from transplant
To analyze the role of Antiviral prophylaxis and the influence in the appearance of infection or disease by CMV.	Indication of Antiviral prophylaxis appearance of infection or disease by CMV.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant
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.	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.	Up to 12 moths from transplant

Collaborators and Investigators

• Sponsor: Sociedad Española de Trasplante
• Collaborators: Roche Farma, S.A
• Investigators: Principal Investigator: Gonzalo Gómez, MD, Hospital Son Espases; Study Chair: José María Aguado, MD, Hospital Universitario 12 de Octubre; Study Chair: Daniel Serón, MD, Hospital Universitario Vall D´Hebron; 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 Marques 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´Hebron; 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: 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

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): February 15, 2017
• Study Completion (Actual): February 15, 2017

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 13, 2017
• First Posted (Actual): March 20, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; Parasitic Diseases; Infections; Communicable Diseases; Opportunistic Infections
• Other Study ID Numbers: SET-INF-2014-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No