Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis

NCT04706507 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: RG11212191UG3HL147011-01A110547
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 20

Brief Summary

This is a phase 3 study designed to evaluate whether the administration of ganciclovir increases ventilator-free days in immunocompetent patients with sepsis associated acute respiratory failure. Our hypothesis is that IV ganciclovir administered early in critical illness will effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory failure thereby leading to improved clinical outcomes

Conditions

Acute Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure

  To evaluate whether administration of ganciclovir increases respiratory-support-free days in immunocompetent patients with sepsis-associated acute respiratory failure. The outcome is the number of days the participant is not on respiratory support in the first 28 study days. This outcome uses the last-off approach to calculate the number of respiratory support days. The number of support days after calculated from the last day the participant was on respiratory support.

  up to 28 days

Secondary Outcomes (10)

• To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure.

  up to 28 study days

• To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure

  up to 28 days

• To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.

  at study day 28

• To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.

  at the final study visit (day 180)

• To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.

  up to 28 days

Study Arms (2)

IV Ganciclovir

EXPERIMENTAL

5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge

Drug: IV Ganciclovir

Placebo

PLACEBO COMPARATOR

normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge

Drug: Normal saline

Interventions

IV Ganciclovir DRUG

For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Also known as: Cytovene

IV Ganciclovir

Normal saline DRUG

For first 5 days, dosing of intravenous saline is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV saline 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject/next of kin informed consent
• Age \> 18 years
• CMV IgG seropositive by lateral flow assay (LFA) or standard serologic methods
• Receiving care in an ICU
• Acute respiratory failure as defined in Section 4.1.1.
• Expected to require respiratory support for at least 2 more days after randomization
• Infection confirmed or suspected by the treating clinician and felt to be the source of acute respiratory failure (Respiratory failure associated with infection confers at least 2 SOFA points above assumed baseline SOFA score of 0, thereby meeting Sepsis-3 definition).

You may not qualify if:

• Known or suspected immunosuppression, including:
• HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment)
• stem cell transplantation:
• within 6 months after autologous transplantation or
• within 1 years after allogeneic transplantation (regardless of immunosuppression)
• greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease) Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization.
• solid organ transplantation with receipt of systemic immunosuppression (any time)
• cytotoxic anti-cancer chemotherapy within the past three months (Note: next-of-kin estimate is acceptable)
• congenital immunodeficiency requiring antimicrobial prophylaxis (e.g. TMP-SMX, dapsone, antifungal drugs, intravenous immunoglobulin)
• receipt of one or more of the following in the indicated time period (see Appendix C):
• within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies, or other immunosuppressive drugs associated with CMV reactivation Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix C for commonly prescribed immunosuppressive agents. Information on the use of biologics with moderate immunosuppressive effect but no known effect on CMV are permitted and will be recorded in the CRFs.
• Expected to survive \< 72 hours (in the opinion of the investigator)
• Has been hospitalized for \> 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable).
• Pregnant or breastfeeding (either currently or expected within one month). Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization \[hysterectomy, tubal ligation, oophorectomy\]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable.
• Absolute neutrophil count \< 1,000/mm3 (if no ANC value is available, the WBC must be \> 2500/mm3)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (20)

University of Colorado Denver

Denver, Colorado, 80204, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5360, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Montefioure Medical Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

Wakeforest University, School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45221, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical College of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin School of Medicine & Public Health

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Ganciclovir; Saline Solution

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Michael J. Boeckh
• Organization: Fred Hutch Cancer Center

mboeckh@fredhutch.org

2066676706

Study Officials

• Michael Boeckh, MD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Vaccine and Infectious Disease Division, Fred Hutch

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: January 12, 2021
• Study Start: June 29, 2021
• Primary Completion: October 25, 2024
• Study Completion: April 8, 2025
• Last Updated: December 12, 2025
• Results First Posted: December 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)