Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03699254
Recruitment Status : Recruiting
First Posted : October 9, 2018
Last Update Posted : November 14, 2019
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Maimónides Biomedical Research Institute of Córdoba

Brief Summary:
To assess the efficacy of reduced duration prophylaxis followed by immuno-guided prophylaxis to prevent cytomegalovirus disease.

Condition or disease Intervention/treatment Phase
Transplantation Infection Cytomegalovirus Infections Drug: Valganciclovir Drug: Ganciclovir Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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.
Actual Study Start Date : April 5, 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Active Comparator: Control

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).
Drug: Valganciclovir

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.

Other Name: Valcyte

Drug: Ganciclovir

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.

Other Name: Cymevene

Experimental: Experimental

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.
Drug: Valganciclovir

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.

Other Name: Valcyte

Drug: Ganciclovir

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.

Other Name: Cymevene




Primary Outcome Measures :
  1. Cytomegalovirus disease incidence rate at 18 months after lung transplantation. [ Time Frame: 18 months after subject's transplantation. ]
    Cytomegalovirus disease incidence rate at 18 months after lung transplantation.


Secondary Outcome Measures :
  1. INFG cut-off point other than 0.2 IU/mL [ Time Frame: 18 months after subject's transplantation. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03699254


Contacts
Layout table for location contacts
Contact: Aurora Páez Vega 0034957011040 aurora.paez@imibic.org

Locations
Layout table for location information
Spain
Hospital Universitario Marques de Valdecilla Recruiting
Santander, Cantabria, Spain, 39008
Contact: David Iturbe Fernández, MD         
Principal Investigator: David Iturbe Fernández, MD         
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Piedad Ussetti Gil, MD         
Principal Investigator: Piedad Ussetti Gil, MD         
Hospital Universitario de A Coruña Recruiting
A Coruña, Spain, 15006
Contact: Isabel Otero González, MD         
Principal Investigator: Isabel Otero González, MD         
Hospital Universitario Vall D'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Victor Monforte Torres, MD         
Principal Investigator: Victor Monforte Torres, MD         
Hospital Univesitario Reina Sofía Recruiting
Córdoba, Spain, 14004
Contact: Aurora Páez Vega    0034957011040    aurora.paez@imibic.org   
Principal Investigator: Julián De la Torre Cisneros, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Rodrigo Alonso Moralejo, MD         
Principal Investigator: Rodrigo Alonso Moralejo, MD         
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46026
Contact: Amparo Pastor Colom, MD         
Principal Investigator: Amparo Pastor Colom, MD         
Sponsors and Collaborators
Maimónides Biomedical Research Institute of Córdoba
Instituto de Salud Carlos III
Investigators
Layout table for investigator information
Principal Investigator: Julián de la Torre Cisneros, MD Hospital Universitario Reina Sofía

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Maimónides Biomedical Research Institute of Córdoba
ClinicalTrials.gov Identifier: NCT03699254    
Other Study ID Numbers: CYTOCOR
2018-003300-39 ( EudraCT Number )
First Posted: October 9, 2018    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: The data will be available beginning 9 months and ending 36 months following article publication.
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.

Layout table for additional information
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
Keywords provided by Maimónides Biomedical Research Institute of Córdoba:
Lung transplantation
Cytomegalovirus infection
Specific immunity
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Ganciclovir
Valganciclovir
Ganciclovir triphosphate
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action