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

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

Detailed Description
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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.

Official Title
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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.

Conditions
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Transplantation Infection, Cytomegalovirus Infections

Intervention / Treatment
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* Drug: Valganciclovir
* Drug: Ganciclovir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>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<br>* 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.<br>* Other names: Valcyte;Drug: Ganciclovir<br>* 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.<br>* Other names: Cymevene;|
| Experimental: Experimental<br>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<br>* 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.<br>* Other names: Valcyte;Drug: Ganciclovir<br>* 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.<br>* Other names: Cymevene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 18 months after subject's transplantation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung transplantation, Cytomegalovirus infection, Specific immunity