CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")

NCT01552369 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 11-0073
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 6

Brief Summary

This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients. Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests). A minimum of 176 subjects will be enrolled in the study. The study duration is 7 years. The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.

Conditions

Cytomegalovirus Infection

Keywords

CMV; cytomegalovirus infections; ganciclovir; liver transplant; preemptive therapy; prophylaxis; valganciclovir

Outcome Measures

Primary Outcomes (1)

• Incidence of Cytomegalovirus (CMV) Disease.

  CMV disease as verified by an independent end point committee

  365 days post-transplant

Secondary Outcomes (10)

• All-cause Mortality

  Up to 365 days post-transplant

• Incidence of Allograft Rejection

  Up to 365 days post-transplant

• Graft Loss

  Up to 365 days post-transplant

• Late-onset CMV Disease

  Up to 365 days post-transplant

• Bacterial Infections

  Up to 365 days post-transplant

Study Arms (2)

Preemptive Therapy

EXPERIMENTAL

900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. n=88

Drug: Valganciclovir

Prophylaxis

ACTIVE COMPARATOR

900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=88

Drug: Valganciclovir

Interventions

Valganciclovir DRUG

Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis. Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.

Preemptive Therapy; Prophylaxis

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be \> / = 18 years of age.
• Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).
• Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.
• Have absolute neutrophil count \> 1000/µL at randomization.
• \- If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.
• \-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.
• Subject or legally authorized representative has provided written informed consent.

You may not qualify if:

• Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.
• Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.
• Be breast-feeding mother.
• Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).
• Be undergoing multi organ transplant or have undergone prior organ transplant.
• Have expected life expectancy of less than 72 hours.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Ronald Reagan University of California Los Angeles Medical Center

Los Angeles, California, 90095-8358, United States

Location

Emory Clinic - Transplant Center

Atlanta, Georgia, 30322-1013, United States

Location

Mayo Clinic, Rochester - Infectious Diseases

Rochester, Minnesota, 55905-0001, United States

Location

Mount Sinai School of Medicine - Medicine - Infectious Diseases

New York, New York, 10029-6504, United States

Location

University of Pittsburgh - Medicine - Infectious Diseases

Pittsburgh, Pennsylvania, 15213-3403, United States

Location

University of Washington - Medicine

Seattle, Washington, 98195-7110, United States

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

• Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy. J Infect Dis. 2021 Mar 29;223(6):1073-1077. doi: 10.1093/infdis/jiaa470.

  PMID: 32726431 DERIVED

• Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Stevens-Ayers T, Edmison B, Boeckh M, Limaye AP. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1378-1387. doi: 10.1001/jama.2020.3138.

  PMID: 32286644 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Multiple Acyl Coenzyme A Dehydrogenase Deficiency

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Nina Singh, MD
• Organization: University of Pittsburgh - Medicine - Infectious Diseases

nis5@pitt.edu

412-360-1688

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: March 13, 2012
• Study Start: October 29, 2012
• Primary Completion: June 22, 2018
• Study Completion: June 22, 2018
• Last Updated: August 26, 2021
• Results First Posted: July 2, 2019

Record last verified: 2018-03-22

Locations

US (6)