Prophylaxis With Ganciclovir Improves Graft Survival in Renal Allograft Recipients

Cytomegalovirus Infection Clinical Trial

Official title:

Open, Randomised Study Comparing Preemptive Therapy With Intravenous Ganciclovir With and Without Additional Oral Ganciclovir for CMV Prophylaxis in Immunosuppressed Renal Transplant Patients Receiving Monitoring of CMV Viral Load

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00373165
• Other study ID #: ML19827
• Status: Completed
• Phase: Phase 4
• First received: September 5, 2006
• Last updated: September 12, 2006
• Start date: August 2000
• Est. completion date: October 2003

Study information

• Verified date: September 2006
• Source: Lower Saxony Center for Nephrology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Study Phase: IV

Study Type: Open-label, multicenter, randomised clinical trial with two arms stratified for an intensified immunosuppressive regimen in patients at high risk for acute rejection.

Study Description: 148 kidney transplant recipients at risk for CMV disease were randomized and treated with ganciclovir capsules for 3 months (Group A, prophylaxis, N=74) or received ganciclovir IV only in case of proven CMV viral load (Group B, preemptive therapy, N=74). Initially, a 2 months follow up was planned in this trial. However, the study group decided to offer a longterm follow up to all patients and amended the protocol, respectively.

The aim of the study was to identify the most efficacious way to prevent renal transplant recipients from CMV disease and to find out, if one of these two strategies may increase graft or patient survival. Therefore, both wellknown approaches of CMV prevention were compared in two study groups:

Prophylaxis (Group A): Oral primary prophylaxis with ganciclovir capsules was started directly after transplantation and performed until day 90. In case of CMV infection (proven CMV viral load) or symptomatic CMV disease, treatment with ganciclovir IV was initiated.

Preemptive Therapy (Group B): No oral primary prophylaxis was given. Treatment with ganciclovir IV was given to patients with proven CMV viral load (CMV infection or CMV disease) only.

Description:

Disease Background: More than 60 % of adult people are asymptomatically infected with cytomegalovirus (CMV). Due to immunosuppressive therapy, renal graft recipients are at risk for CMV infection and life-threatening disease. CMV can cause a variety of symptoms in the immunocompromised host, including CMV retinitis, pneumonia or colitis. After grafting, CMV disease most commonly occurs in the transplanted organ and can trigger graft dysfunction and acute rejection. Therefore, prophylaxis or preemptive therapy should be used in order to prevent graft recipients from CMV disease.

• CMV prophylaxis means the administration of antiviral agents to all patients at risk for CMV disease, directly after transplantation, i.e. for 3 months. Prophylaxis is in particular used for patients at high risk for CMV disease.

• CMV preemptive therapy (or targeted prophylaxis) means CMV monitoring and initiation of induction therapy with antiviral agents in patients with proven CMV viral load only (CMV infection). This prevents non-infected patients from being exposed to antiviral drugs and the related side effects like neutropenia or renal toxicity. Preemptive therapy is in particular used for patients at lower or moderate risk for CMV disease.

Study Description: 148 kidney transplant recipients at risk for CMV disease were randomized and treated with ganciclovir capsules for 3 months (Group A, prophylaxis, N=74) or received ganciclovir IV only in case of proven CMV viral load (Group B, preemptive therapy, N=74). Initially, a 2 months follow up was planned in this trial. However, the study group decided to offer a longterm follow up to all patients and amended the protocol, respectively.

The aim of the study was to identify the most efficacious way to prevent renal transplant recipients from CMV disease and to find out, if one of these two strategies may increase graft or patient survival. Therefore, both wellknown approaches of CMV prevention were compared in two study groups:

Prophylaxis (Group A): Oral primary prophylaxis with ganciclovir capsules was started directly after transplantation and performed until day 90. In case of CMV infection (proven CMV viral load) or symptomatic CMV disease, treatment with ganciclovir IV was initiated.

Preemptive Therapy (Group B): No oral primary prophylaxis was given. Treatment with ganciclovir IV was given to patients with proven CMV viral load (CMV infection or CMV disease) only.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Kidney transplant recipients after living or postmortal donation

• CMV seropositive donor or recipient of the kidney transplant: D+/R-, D+/R+ or D-/R+

• Laboratory parameters: 50.000/ml thrombocytes and/or 1000/ml neutrophils

• Immunosuppression including MMF

Main Exclusion Criteria:

• Woman who are pregnant, breastfeeding or using unreliable birth control methods

• Forbidden concomitant medications during the 12 month observation period of the study are:

• Virustatic drugs, active against CMV: Foscarnet, Cidofovir (HPMPC), Acyclovir, Valaciclovir, Famciclovir/Penciclovir, Lobucavir, Antisense compound

• Antimetabolites: Fluorouracil, Mercaptopurine, Methotrexate, Thioguanine, Hydroxurea

• Alkylating substances: Busulfan, Carmustine, Chlorambucil, Cisplatin, Cyclophosphamide, Dacarbazine (DTIC), Lomustine, Mechlormethamine, Melphalan, Streptozotocin, Tiothepa, Uracil mustard

• anti CMV immunoglobulins (except in the case of signs of CMV infection) such as anti CMV hyperimmunoglobulins and immunoglobulins

• Known hypersensitivity to ganciclovir

• Patients with active CMV infection or positive viraemia at randomization

• Severe gastro-intestinal diseases which may interfere with the oral resorption of ganciclovir

• Conversion of immunosuppression (Replacement of MMF)

• Participation in another clinical drug trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infection
• Cytomegalovirus Infections
• DNA Virus Infection
• DNA Virus Infections
• Herpesviridae Infections
• Infection
• Virus Diseases

Intervention

Drug:
• Ganciclovir

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lower Saxony Center for Nephrology

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The impact of CMV infection on graft function, incidence of CMV infection and creatinine clearance in both study groups at month 12. long-term graft and patient survival. Neutrophil counts and creatinine clearance were measured on a regular basis.