Valganciclovir for Treatment of Cytomegalovirus Infection in Solid Organ Transplant Patients

Phase IV.II Pilot Study of Treatment of Cytomegalovirus Infection With a Brief Induction With Ganciclovir i.v. Followed by Valganciclovir Oral in Solid Organ Transplant Patients.

The objectives of this study were:

1. To demonstrate the efficacy/safety of a short therapeutic strategy of treatment of CMV infection/disease in SOT patients (kidney, liver and heart recipients) based on 21 days of treatment.
2. To compare the exposure to ganciclovir, at steady state, after oral valganciclovir with respect to ganciclovir given intravenously (i.v.).
3. Evaluate the security of this treatment with valganciclovir.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Drug: Single arm (ganciclovir and valganciclovir)

Detailed Description

SOT recipients (kidney, liver and heart transplant) presenting CMV infection or disease were eligible for inclusion if they were ≥18 years of age and presented a positive CMV antigenemia (pp65) defined as ≥ 20positive cells/105 peripherical blood mononuclear cells (PBMC). Patients excluded were those with severe CMV tissue invasive disease, unable to receive oral medication, absolute neutrophil counts less than 500/ mm3, platelets <25000 platelets/mm3, Hemoglobin< 80g/l or estimated glomerular filtration rate< 10 mL/min (according to the Cockcroft-Gault formula).

Patients received a short induction treatment with ganciclovir i.v (Cymevene®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) at the dose of 5 mg/kg/12h, by a peripherical vein infusion of one hour, during 5 days followed by treatment with oral valganciclovir (Valcyte®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) at 900 mg/12h during 16 days, after meals, until complete a total of 21 days of treatment. In patients with impaired renal function ganciclovir i.v. and oral valganciclovir doses were adjusted at each visit according to estimated Glomerular Filtration Rate (GFR) by Cockcroft-Gault equation, as recommended by the manufacturer.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelone
    • L'Hospitalet de Llobregat, Barcelone, Spain, 08907
      • Hospital Universitari Bellvitge- Transplant Departments (Liver, Heart and Kidney)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥18 years of age, solid organ transplant recipients.
• presented a CMV infection demonstrated by CMV antigenemia (pp65) defined as ≥ 20positive cells/105 peripherical blood mononuclear cells (PBMC).
• gave written informed consent.

Exclusion Criteria:

• HIV patients.
• Multiorganic transplant.
• Severe CMV tissue invasive disease.
• Unable to receive oral medication.
• absolute neutrophil counts less than 500/ mm3.
• Platelets <25000 platelets/mm3.
• Hemoglobin< 80g/l.
• Estimated glomerular filtration rate< 10 mL/min (according to the Cockcroft-Gault formula)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Single arm; Patients received a short induction of IV ganciclovir (Cymevene®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) at 5 mg/kg bid for 5 days (1 hour infusion) , followed by treatment with oral valganciclovir (Valcyte®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) at 900 mg bid (after meals) for 16 days up to complete 21 days of treatment. In patients with impaired renal function, IV ganciclovir and oral valganciclovir doses were adjusted at each visit according to estimated GFR (Cockcroft-Gault equation)

Drug: Single arm (ganciclovir and valganciclovir); Patients received a short induction of IV ganciclovir at 5 mg/kg bid for 5 days (1 hour infusion) , followed by treatment with oral valganciclovir at 900 mg bid (after meals) for 16 days up to complet 21 days of treatment. In patients with impaired renal function, IV ganciclovir and oral valganciclovir doses were adjusted at each visit according to estimated GFR (Cockroft-Gault equation); Other Names: Ganciclovir (Cymevene®); Valganciclovir (Valcyte®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dissapeareance of CMV (pp65) antigenemia, determined in peripheral blood mononuclear cells (PBMC).	Baseline, day 5, 10, 15, 21 of treatment and day 30, 60 and 90 of follow-up.

Secondary Outcome Measures

Outcome Measure	Time Frame
Dissapareance of Cytomegalovirus viremia measured by PCR, determined in plasma samples.	Basal, day 5, 10, 15 and 21 of treatment and 30, 60 and 90 of treatment.
Area under the curve (AUC) of Ganciclovir after ganciclovir i.v. and valganciclovir oral in steady state.	Day 5 (ganciclovir i.v) and day 15 (valganciclovir oral)

Collaborators and Investigators

• Sponsor: Salvador Gil-Vernet
• Collaborators: Roche Pharma AG
• Investigators: Study Chair: Salvador - Gil-Vernet, Medicine, Nephrology Department. Hospital Universitari of Bellvitge

Publications and helpful links

General Publications

• Caldes A, Colom H, Armendariz Y, Garrido MJ, Troconiz IF, Gil-Vernet S, Lloberas N, Pou L, Peraire C, Grinyo JM. Population pharmacokinetics of ganciclovir after intravenous ganciclovir and oral valganciclovir administration in solid organ transplant patients infected with cytomegalovirus. Antimicrob Agents Chemother. 2009 Nov;53(11):4816-24. doi: 10.1128/AAC.00085-09. Epub 2009 Sep 8.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: August 5, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (ESTIMATE): August 8, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 21, 2011
• Last Update Submitted That Met QC Criteria: September 19, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Transplant; Ganciclovir; Solid organ transplantation; Valganciclovir
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Valganciclovir; Ganciclovir; Ganciclovir triphosphate
• Other Study ID Numbers: VALGAN-03