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

Sponsor

Maimónides Biomedical Research Institute of Córdoba (Other)

Overall Status

Recruiting

CT.gov ID

NCT03699254

Collaborator

Instituto de Salud Carlos III (Other)

150

Enrollment

Locations

Arms

50.9

Anticipated Duration (Months)

21.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Apr 5, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Jul 1, 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 Names: 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 Names: 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 Names: 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 Names: Cymevene

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 Names:

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 Names:

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

Other Names:

Valcyte

Drug: Ganciclovir

Other Names:

Cymevene

Outcome Measures

Primary Outcome Measures

Cytomegalovirus disease incidence rate at 18 months after lung transplantation. [18 months after subject's transplantation.]
Cytomegalovirus disease incidence rate at 18 months after lung transplantation.

Secondary Outcome Measures

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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
2	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
3	Hospital Universitario de A Coruña	A Coruña		Spain	15006
4	Hospital Universitario Vall D'Hebron	Barcelona		Spain	08035
5	Hospital Univesitario Reina Sofía	Córdoba		Spain	14004
6	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
7	Hospital Universitario La Fe	Valencia		Spain	46026