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

NCT ID: NCT03699254

Last Updated: 2023-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-05
• Study Completion Date: 2023-05-29

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.

Conditions

Transplantation Infection; Cytomegalovirus Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Valganciclovir

Intervention Type: DRUG

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.

Ganciclovir

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Valganciclovir

Intervention Type: DRUG

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.

Ganciclovir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Valcyte; Cymevene

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Maimónides Biomedical Research Institute of Córdoba

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julián de la Torre Cisneros, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Reina Sofía

Locations

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Universitario de A Coruña

A Coruña, , Spain

Hospital Universitario Vall D'Hebron

Barcelona, , Spain

Hospital Univesitario Reina Sofía

Córdoba, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Countries

Spain

References

Paez-Vega A, Vaquero-Barrios JM, Ruiz-Arabi E, Iturbe-Fernandez D, Alonso R, Ussetti-Gil P, Monforte V, Pastor A, Fernandez-Moreno R, Mora VM, Erro-Iribarren M, Quezada CA, Berastegui C, Cifrian-Martinez JM, Cano A, Caston JJ, Machuca I, Lobo-Acosta MA, Gutierrez-Gutierrez B, Cantisan S, Torre-Cisneros J; CYTOCOR study group. Safety and efficacy of immunoguided prophylaxis for cytomegalovirus disease in low-risk lung transplant recipients in Spain: a multicentre, open-label, randomised, phase 3, noninferiority trial. Lancet Reg Health Eur. 2025 Mar 26;52:101268. doi: 10.1016/j.lanepe.2025.101268. eCollection 2025 May.

Reference Type: DERIVED

PMID: 40224372 (View on PubMed)

Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.

Reference Type: DERIVED

PMID: 39807668 (View on PubMed)

Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

Reference Type: DERIVED

PMID: 38700045 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32504089 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31420397 (View on PubMed)

Other Identifiers

2018-003300-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CYTOCOR

Identifier Type: -

Identifier Source: org_study_id