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

NCT03699254 | Completed Phase 3

• 2 other identifiers: CYTOCOR2018-003300-39
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Transplantation Infection; Cytomegalovirus Infections

Keywords

Lung transplantation; Cytomegalovirus infection; Specific immunity

Outcome Measures

Primary Outcomes (1)

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

  Cytomegalovirus disease incidence rate at 18 months after lung transplantation.

  18 months after subject's transplantation.

Secondary Outcomes (1)

• INFG cut-off point other than 0.2 IU/mL

  18 months after subject's transplantation.

Study Arms (2)

Control

ACTIVE COMPARATOR

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; Drug: Ganciclovir

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; Drug: Ganciclovir

Interventions

Valganciclovir 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.

Also known as: Valcyte

Control; Experimental

Ganciclovir 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.

Also known as: Cymevene

Control; Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maimónides Biomedical Research Institute of Córdoba: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (7)

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario de A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Univesitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Related Publications (5)

• 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.

  PMID: 40224372 DERIVED

• 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.

  PMID: 39807668 DERIVED

• 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.

  PMID: 38700045 DERIVED

• 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.

  PMID: 32504089 DERIVED

• 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.

  PMID: 31420397 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

Valganciclovir; Ganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Julián de la Torre Cisneros, MD

  Hospital Universitario Reina Sofía

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 9, 2018
• Study Start: April 5, 2019
• Primary Completion: May 29, 2023
• Study Completion: May 29, 2023
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

ES (7)