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

• ClinicalTrials.gov Identifier: NCT03699254
• Recruitment Status: Recruiting
• First Posted: October 9, 2018
• Last Update Posted: November 14, 2019
• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Collaborator: Instituto de Salud Carlos III
• Information provided by (Responsible Party): Maimónides Biomedical Research Institute of Córdoba

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

Contact: Aurora Páez Vega; 0034957011040; aurora.paez@imibic.org

Locations

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

• Principal Investigator: Julián de la Torre Cisneros, MD; Hospital Universitario Reina Sofía

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paez-Vega A, Cantisan S, Vaquero JM, Vidal E, Luque-Pineda A, Lobo-Acosta MÁ, Pérez 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.

• 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
• 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.

• 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:

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