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

Cytomegalovirus Infection Clinical Trial

Official title:

Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01552369
• Other study ID #: 11-0073
• Status: Completed
• Phase: Phase 4
• Start date: October 29, 2012
• Est. completion date: June 22, 2018

Study information

• Verified date: March 22, 2018
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (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 for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests. Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality). Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group. Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment. Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant. A minimum of 176 subjects will be enrolled in the study. Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176. Subjects will be randomized into one of the two groups in 1:1 ratio. 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. The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: June 22, 2018
• Est. primary completion date: June 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Be > / = 18 years of age.

2. Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).

3. Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.

4. Have absolute neutrophil count > 1000/µL at randomization.

5. - 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.

6. Subject or legally authorized representative has provided written informed consent.

Exclusion Criteria:

1. 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.

2. Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.

3. Be breast-feeding mother.

4. Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).

5. Be undergoing multi organ transplant or have undergone prior organ transplant.

6. Have expected life expectancy of less than 72 hours.

Related Conditions & MeSH terms

• Cytomegalovirus Infection
• Cytomegalovirus Infections

Intervention

Drug:
• Valganciclovir
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.

Locations

Country	Name	City	State
United States	Emory Clinic - Transplant Center	Atlanta	Georgia
United States	Ronald Reagan University of California Los Angeles Medical Center	Los Angeles	California
United States	Mount Sinai School of Medicine - Medicine - Infectious Diseases	New York	New York
United States	University of Pittsburgh - Medicine - Infectious Diseases	Pittsburgh	Pennsylvania
United States	Mayo Clinic, Rochester - Infectious Diseases	Rochester	Minnesota
United States	University of Washington - Medicine	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Cytomegalovirus (CMV) Disease.	CMV disease as verified by an independent end point committee	365 days post-transplant
Secondary	All-cause Mortality	Survival probability at 1 year	Up to 365 days post-transplant
Secondary	Incidence of Allograft Rejection	Number of subjects with allograft rejection	Up to 365 days post-transplant
Secondary	Graft Loss	Incidence of graft loss (re-transplantation)	Up to 365 days post-transplant
Secondary	Late-onset CMV Disease	Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee	Up to 365 days post-transplant
Secondary	Bacterial Infections	Incidence of bacterial opportunistic infections	Up to 365 days post-transplant
Secondary	Major Fungal Infections	Opportunistic fungal infections	Up to 365 days post-transplant
Secondary	Major Non-CMV Viral Infections	Incidence of non-CMV viral infections	Up to 365 days post-transplant
Secondary	Neutropenia	Incidence of neutropenia less than 1000/µL while on valganciclovir treatment	Day 1 through Day 107
Secondary	Neutropenia Less Than 500	ANC less than 500 while on valganciclovir	prior to day 107
Secondary	Hematopoietic Growth Factors	Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.	Day 1 through Day 107