A Study of Valcyte (Valganciclovir) CMV Prophylaxis After Renal Transplantation

NCT00372229 | Completed Phase 3 Results

• 1 other identifier: ML19313
• Study Type: interventional
• Target: 299
• Locations: 2 countries
• Sites: 24

Brief Summary

This 2 arm study will compare the efficacy of 100 days of Valcyte (900mg po daily) prophylaxis with that of no prophylaxis, under the condition of pre-emptive therapy of active CMV infection, in CMV positive renal transplant recipients. The influence of the two prevention concepts on the occurrence of direct and indirect effects of active CMV infections will be compared. The anticipated time on study treatment is 3 months-1 year, and the target sample size is 100-500 individuals.

Conditions

Cytomegalovirus Infections

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Active Cytomegalovirus (CMV) Infection Within 12 Months

  Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml).

  Up to 12 months

• Percentage of Participants With CMV Disease Within 12 Months Including CMV Syndrome and Tissue Invasive Disease

  CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced \>50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid \[DNA\] by immunostaining or hybridization, respectively), cerebral spinal fluid \[CSF\]) and/or relevant symptoms or signs of organ dysfunction.

  Up to 12 months

• Urine Proteomic Pattern at Month 12

  Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. Urine proteomic pattern was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration.

  Up to 12 months

• Percentage of Participants With Graft Loss at Month 84

  Up to 84 months

Secondary Outcomes (38)

• Percentage of Participants With CMV Syndrome Within 12 Months

  Up to 12 months

• Percentage of Participants With CMV Tissue Invasive Disease Within 12 Months

  Up to 12 months

• Time to Occurrence of First Viremia Within 12 Months

  Up to 12 months

• Viral Burden at Viremia

  Up to 12 months

• Creatinine Clearance at Month 12

  Up to 12 months

Study Arms (2)

Valganciclovir Cytomegalovirus (CMV) Prophylaxis

EXPERIMENTAL

Drug: Valganciclovir CMV Prophylaxis

Pre-emptive CMV Therapy

ACTIVE COMPARATOR

Drug: Valganciclovir (Pre-emptive CMV Therapy); Drug: Ganciclovir

Interventions

Valganciclovir CMV Prophylaxis DRUG

900 mg valganciclovir, taken orally once daily, adjusted to renal function starting within 14 days of transplantation until Day 100 after transplantation.

Also known as: Valcyte

Valganciclovir Cytomegalovirus (CMV) Prophylaxis

Valganciclovir (Pre-emptive CMV Therapy) DRUG

If plasma polymerase chain reaction (PCR) ≥ 400 CMV copies/millilitre, then 1800 mg valganciclovir per day adjusted to renal function for at least 14 days until the second negative PCR (below 400 copies/ml) followed by secondary prophylaxis for 28 days with 900 mg valganciclovir adjusted to renal function. If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site's standard, instead of valganciclovir.

Also known as: Valcyte

Pre-emptive CMV Therapy

Ganciclovir DRUG

If CMV disease or no response to valganciclovir treatment after 14 days (not falling viral load), then intravenous (IV) ganciclovir or additional appropriate therapy could have been administered according to the local site's standard, instead of valganciclovir.

Pre-emptive CMV Therapy

Eligibility Criteria

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

You may qualify if:

• primary or secondary renal allograft within preceding 14 days;
• IgG seropositive for CMV;
• receiving immunosuppressive therapy.

You may not qualify if:

• active CMV infection;
• current/history of malignancy;
• acute steroid resistant rejection episode since transplantation.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (24)

Unknown Facility

Innsbruck, 6020, Austria

Location

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

Aachen, 52057, Germany

Location

Unknown Facility

Berlin, 12203, Germany

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Unknown Facility

Berlin, 13353, Germany

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Unknown Facility

Bremen, 28205, Germany

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Unknown Facility

Cologne, 50937, Germany

Location

Unknown Facility

Düsseldorf, 40225, Germany

Location

Unknown Facility

Erlangen, 91054, Germany

Location

Unknown Facility

Essen, 45122, Germany

Location

Unknown Facility

Frankfurt, 60596, Germany

Location

Unknown Facility

Freiburg im Breisgau, 79106, Germany

Location

Unknown Facility

Hamburg, 20246, Germany

Location

Unknown Facility

Hannoversch Münden, 34346, Germany

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Jena, 07747, Germany

Location

Unknown Facility

Leipzig, 04103, Germany

Location

Unknown Facility

Lübeck, 23562, Germany

Location

Unknown Facility

München, 81377, Germany

Location

Unknown Facility

München, 81675, Germany

Location

Unknown Facility

Münster, 48149, Germany

Location

Unknown Facility

Regensburg, 93053, Germany

Location

Unknown Facility

Tübingen, 72076, Germany

Location

Unknown Facility

Würzburg, 97080, Germany

Location

Related Publications (4)

• 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

• Mazzola P, Schaeffeler E, Witzke O, Nitschke M, Kliem V, Zortel M, Wagner EM, Schwab M, Hauser IA. No association of genetic variants in TLR4, TNF-alpha, IL10, IFN-gamma, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection-Subanalysis of the prospective randomised VIPP study. PLoS One. 2021 Apr 16;16(4):e0246118. doi: 10.1371/journal.pone.0246118. eCollection 2021.

  PMID: 33861738 DERIVED

• Witzke O, Nitschke M, Bartels M, Wolters H, Wolf G, Reinke P, Hauser IA, Alshuth U, Kliem V. Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: Long-term Results After 7 Years of a Randomized Clinical Trial. Transplantation. 2018 May;102(5):876-882. doi: 10.1097/TP.0000000000002024.

  PMID: 29166336 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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 5, 2006
• First Posted: September 6, 2006
• Study Start: May 1, 2006
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 11, 2020
• Results First Posted: March 11, 2020

Record last verified: 2020-02

Locations

AU (2); DE (22)