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Clinical Trial of Efficacy and Safety of the Combination of Reduced Duration Prophylaxis Followed by Immuno-guided Prophylaxis in Lung Transplant Recipients. (CYTOCOR)

Primary Purpose

Transplantation Infection, Cytomegalovirus Infections

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Valganciclovir
Ganciclovir
Sponsored by
Maimónides Biomedical Research Institute of Córdoba
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Transplantation Infection focused on measuring Lung transplantation, Cytomegalovirus infection, Specific immunity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects with cytomegalovirus positive serology who underwent lung transplantation.
  • Subjects of 18 years of age or older.
  • Expected valgancilovir prophylactic treatment of 6 months after transplantation.
  • Patients who have signed the informed consent form.

Exclusion Criteria:

  • HIV infected subjects.
  • Subjects unable to comply with the protocolo follow-up visits.
  • Subjects who underwent multivisceral transplant.
  • Pregnant and/or lactating women.
  • Intolerance to Valganciclovir/Ganciclovir treatment.

Sites / Locations

  • Hospital Universitario Marques de Valdecilla
  • Hospital Universitario Puerta de Hierro
  • Hospital Universitario de A Coruña
  • Hospital Universitario Vall D'Hebron
  • Hospital Univesitario Reina Sofía
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario La Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control

Experimental

Arm Description

Control Group (universal prophylaxis + pre-emptive therapy; 6+6): The recommendation of the Spanish Consensus Document will be followed according to the strategy described below: Universal prophylaxis with valganciclovir (900 mg/24h, corrected for renal function) up to month +6. The use of associated immunotherapy (e.g., anti-CMV hyperimmune immunoglobulin) will depend on each center's clinical practice. During this period, the treatment of blips of viral replication detected during the usual clinical follow-up of patients will depend oneach center's clinical practice. Pre-emptive therapy guided by viral load from month +6 to month +12. For a viral load above> 38 copies/mL (> 35 IU/mL) and depending on each center's clinical practice, treatment with valganciclovir may be initiated (900 mg/12h, corrected for renal function).

Experimental Group (reduced prophylaxis + immuno-guided prophylaxis; 3+9): Universal prophylaxis with valganciclovir (900 mg/24h, corrected for renal function) up to month +3. The use of associated immunotherapy (e.g., anti-CMV hyperimmune immunoglobulin) will depend oneach center's clinical practice. During this period, the treatment of blips of viral replication detected during the usual clinical follow-up of the patients will depend on the each center's clinical practice. Immuno-guided prophylaxis. This will consist of a monthly determination of cellular immunity by QF-CMV from month +3 to month +12.

Outcomes

Primary Outcome Measures

Cytomegalovirus disease incidence rate at 18 months after lung transplantation.
Cytomegalovirus disease incidence rate at 18 months after lung transplantation.

Secondary Outcome Measures

INFG cut-off point other than 0.2 IU/mL
For patients of the experimental group (3+9) in which immuno-guided prophylaxis is used based on QF-CMV Reactive (cut-off 0.2 IU/mL of IFNG) and who develop CMV disease, a secondary objective will be to assess whether an INFG cut-off point other than 0.2 IU/mL could predict protection against the disease more reliably.

Full Information

First Posted
October 5, 2018
Last Updated
September 14, 2023
Sponsor
Maimónides Biomedical Research Institute of Córdoba
Collaborators
Instituto de Salud Carlos III
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1. Study Identification

Unique Protocol Identification Number
NCT03699254
Brief Title
Clinical Trial of Efficacy and Safety of the Combination of Reduced Duration Prophylaxis Followed by Immuno-guided Prophylaxis in Lung Transplant Recipients.
Acronym
CYTOCOR
Official Title
Efficacy and Safety of the Combination of Reduced Duration Prophylaxis Followed by Immuno-guided Prophylaxis to Prevent Cytomegalovirus Disease in Lung Transplant Recipients (CYTOCOR STUDY): An Open-label, Randomised, Non-inferiority Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
April 5, 2019 (Actual)
Primary Completion Date
May 29, 2023 (Actual)
Study Completion Date
May 29, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maimónides Biomedical Research Institute of Córdoba
Collaborators
Instituto de Salud Carlos III

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the efficacy of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease.
Detailed Description
Prolonged use of antivirals to prevent the development of cytomegalovirus (CMV) disease in lung transplant patients has been shown to have significant side effects, for which alternatives are being sought to reduce their use. The monitoring of cell immunity against CMV could be an alternative as it has shown to be useful in identifying transplant patients at low risk of infection, who could benefit from shorter prophylaxis. The aim of the CYTOCOR study is to demonstrate that the combination of a reduced prophylaxis strategy with subsequent CMV-specific immunological monitoring would allow CMV infection to be controlled in lung transplant patients as effectively as the usual strategy (prophylaxis followed by pre-emptive therapy), while reducing the side effects of antivirals due to the shorter duration of prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transplantation Infection, Cytomegalovirus Infections
Keywords
Lung transplantation, Cytomegalovirus infection, Specific immunity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Active Comparator
Arm Description
Control Group (universal prophylaxis + pre-emptive therapy; 6+6): The recommendation of the Spanish Consensus Document will be followed according to the strategy described below: Universal prophylaxis with valganciclovir (900 mg/24h, corrected for renal function) up to month +6. The use of associated immunotherapy (e.g., anti-CMV hyperimmune immunoglobulin) will depend on each center's clinical practice. During this period, the treatment of blips of viral replication detected during the usual clinical follow-up of patients will depend oneach center's clinical practice. Pre-emptive therapy guided by viral load from month +6 to month +12. For a viral load above> 38 copies/mL (> 35 IU/mL) and depending on each center's clinical practice, treatment with valganciclovir may be initiated (900 mg/12h, corrected for renal function).
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Experimental Group (reduced prophylaxis + immuno-guided prophylaxis; 3+9): Universal prophylaxis with valganciclovir (900 mg/24h, corrected for renal function) up to month +3. The use of associated immunotherapy (e.g., anti-CMV hyperimmune immunoglobulin) will depend oneach center's clinical practice. During this period, the treatment of blips of viral replication detected during the usual clinical follow-up of the patients will depend on the each center's clinical practice. Immuno-guided prophylaxis. This will consist of a monthly determination of cellular immunity by QF-CMV from month +3 to month +12.
Intervention Type
Drug
Intervention Name(s)
Valganciclovir
Other Intervention Name(s)
Valcyte
Intervention Description
Valganciclovir is a L-valyl ester of ganciclovir that exists as a mix of 2 diastereomers. After administration, both are converted to ganciclovir by esterases. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, it inhibits replication of cytomegalovirus. In CMV-infected cells it's phosphorylated (phosphorylation is dependent on the viral kinase and occurs preferentially in virus-infected cells). Ganciclovir activity is due to inhibition of viral DNA synthesis by ganciclovir triphosphate.
Intervention Type
Drug
Intervention Name(s)
Ganciclovir
Other Intervention Name(s)
Cymevene
Intervention Description
Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, it inhibits replication of cytomegalovirus. In CMV-infected cells it's phosphorylated (phosphorylation is dependent on the viral kinase and occurs preferentially in virus-infected cells). Ganciclovir activity is due to inhibition of viral DNA synthesis by ganciclovir triphosphate.
Primary Outcome Measure Information:
Title
Cytomegalovirus disease incidence rate at 18 months after lung transplantation.
Description
Cytomegalovirus disease incidence rate at 18 months after lung transplantation.
Time Frame
18 months after subject's transplantation.
Secondary Outcome Measure Information:
Title
INFG cut-off point other than 0.2 IU/mL
Description
For patients of the experimental group (3+9) in which immuno-guided prophylaxis is used based on QF-CMV Reactive (cut-off 0.2 IU/mL of IFNG) and who develop CMV disease, a secondary objective will be to assess whether an INFG cut-off point other than 0.2 IU/mL could predict protection against the disease more reliably.
Time Frame
18 months after subject's transplantation.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with cytomegalovirus positive serology who underwent lung transplantation. Subjects of 18 years of age or older. Expected valgancilovir prophylactic treatment of 6 months after transplantation. Patients who have signed the informed consent form. Exclusion Criteria: HIV infected subjects. Subjects unable to comply with the protocolo follow-up visits. Subjects who underwent multivisceral transplant. Pregnant and/or lactating women. Intolerance to Valganciclovir/Ganciclovir treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julián de la Torre Cisneros, MD
Organizational Affiliation
Hospital Universitario Reina Sofía
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Universitario de A Coruña
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario Vall D'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Univesitario Reina Sofía
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The individual participant data will be available. Individual parcicipant data that underlie the results reportes in this article, after deidenttification (text, tables, figures and appendices) The other documents that will be available: study protocol, Statistical Analysis Plan, Informed Consent Form. The data will be available beginning 9 months and ending 36 months following article publication. With whom? Researchers who provide a methodologically sound proposal. For what types of analyses? for individual participant data meta-analysis.
IPD Sharing Time Frame
The data will be available beginning 9 months and ending 36 months following article publication.
IPD Sharing Access Criteria
To obtain the data, a proposal must be sent to uicec@imibic.org. To gain access, data requestors will need to sign a data access agreement.
Citations:
PubMed Identifier
32504089
Citation
Gibson L. An Interferon-gamma Release Assay for Evaluation of Cell-mediated Immunity in Infants With Congenital Cytomegalovirus Infection. Clin Infect Dis. 2021 Aug 2;73(3):374-375. doi: 10.1093/cid/ciaa700. No abstract available.
Results Reference
derived
PubMed Identifier
31420397
Citation
Paez-Vega A, Cantisan S, Vaquero JM, Vidal E, Luque-Pineda A, Lobo-Acosta MA, Perez AB, Alonso-Moralejo R, Iturbe D, Monforte V, Otero-Gonzalez I, Pastor A, Ussetti P, Torre-Cisneros J. Efficacy and safety of the combination of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease in lung transplant recipients (CYTOCOR STUDY): an open-label, randomised, non-inferiority clinical trial. BMJ Open. 2019 Aug 15;9(8):e030648. doi: 10.1136/bmjopen-2019-030648.
Results Reference
derived

Learn more about this trial

Clinical Trial of Efficacy and Safety of the Combination of Reduced Duration Prophylaxis Followed by Immuno-guided Prophylaxis in Lung Transplant Recipients.

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