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

Recruitment Status
TERMINATED - HAS RESULTS
(See Contacts and Locations)Verified October 2025 by Fred Hutchinson Cancer Center
Sponsor
Fred Hutchinson Cancer Center
Information Provided by (Responsible Party)
Michael Boeckh
Clinicaltrials.gov Identifier
NCT04706507
Other Study ID Numbers:
RG1121219
First Submitted
December 22, 2020
First Posted
January 11, 2021
Results First Posted
October 24, 2025
Last Update Posted
December 11, 2025
Last Verified
October 2025

ClinicalTrials.gov processed this data on November 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Acute Respiratory Failure
Drug: IV GanciclovirDrug: Normal saline

Study Design

Study TypeInterventional
Actual Enrollment205 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleGanciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
Study Start DateJune 28, 2021
Actual Primary Completion DateOctober 24, 2024
Actual Study Completion DateApril 7, 2025

Groups and Cohorts

Group/CohortIntervention/Treatment
IV Ganciclovir
5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge
Drug: IV Ganciclovir
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.
Placebo
normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge
Drug: Normal saline
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.

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure.
    During the first 28 study days, the number of days the participants are not on mechanical ventilation using the last off approach is compared between the two treatment arms.
  2. 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
    During the first 28 study days, the number of days the participants are not on any respiratory-support is compared between the two treatment arms. Instead of using last-off approach, we will count all the days during 28 days period.
  3. To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.
    This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at 28 days. The hazard ratio and Cox proportional hazards models are used for this endpoint.
  4. To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.
    This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at the end of the study (day 180).
  5. To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
    This endpoint summarizes the days of mechanical ventilation for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded.
  6. To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
    This endpoint summarizes the days of all types of respiratory support for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded.
  7. To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
    The PaO2/FiO2 (P/F) ratio was used to define oxygenation. The P/F ratio was summarized over the first 7 days of the study. The lowest PaO2 value within each study day was reported and used in the oxygenation calculation. If the PaO2 value was not available, an estimate of PaO2 was calculated from the SpO2 lowest value.
  8. To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients.
    During the first 28 study days, the number of days the participants are not in ICU using the last off approach is compared between the two treatment arms.
  9. To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
    CMV DNA detection in plasma and endotracheal aspirate (ETA) by day 28 is defined as positive CMV PCR result from any ETA, plasma, or serum specimen collected through day 28. CMV reactivation by day 28 will be summarized with number of participants with CMV reactivation in two levels: as any detectable CMV DNA (any level) and as high-level reactivation (\>1000 IU/mL) for CMV negative patients at baseline.
  10. To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups.
    During the first 28 days, this endpoint summarizes the number of participants who experienced adverse events (AEs) of severity grade ≥3 and whether any serious adverse events (SAEs) occurred in each study arm.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
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).
Exclusion Criteria
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)
Use of anti-CMV drugs (cidofovir, letermovir, foscarnet, valganciclovir, ganciclovir) within seven (7) days of patient randomization.
Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity or to be associated with significant known hematologic toxicity (prior approval required).
At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation.
Patients with Child Class C Cirrhosis.
Patients with severe (requiring home oxygen) pre-existing interstitial lung disease.
Allergy to ganciclovir
Incarcerated

Contacts and Locations

Sponsors and CollaboratorsFred Hutchinson Cancer Center
Locations
University of Colorado Denver | Denver Colorado, United States, 80204Johns Hopkins University | Baltimore Maryland, United States, 21218Brigham & Women's Hospital | Boston Massachusetts, United States, 02115University of Michigan | Ann Arbor Michigan, United States, 48109-5360Henry Ford Hospital | Detroit Michigan, United States, 48202Washington University | St Louis Missouri, United States, 63130Montefioure Medical Center | The Bronx New York, United States, 10467Duke University | Durham North Carolina, United States, 27708Wakeforest University, School of Medicine | Winston-Salem North Carolina, United States, 27157University of Cincinnati | Cincinnati Ohio, United States, 45221The Cleveland Clinic Foundation | Cleveland Ohio, United States, 44195Ohio State University Medical Center | Columbus Ohio, United States, 43210University of Pittsburgh Medical Center | Pittsburgh Pennsylvania, United States, 15261Medical College of South Carolina | Charleston South Carolina, United States, 29425Vanderbilt University | Nashville Tennessee, United States, 37235Intermountain Medical Center | Murray Utah, United States, 84107University of Vermont College of Medicine | Burlington Vermont, United States, 05405Harborview Medical Center | Seattle Washington, United States, 98104University of Washington Medical Center | Seattle Washington, United States, 98195University of Wisconsin School of Medicine & Public Health | Madison Wisconsin, United States, 53792
Investigators
Principal Investigator: Michael Boeckh, MD, Fred Hutchinson Cancer Center
Study Documents (Full Text)
Documents provided by Fred Hutchinson Cancer Center: Study Protocol and Statistical Analysis Plan: Protocol  July 22, 2025Documents provided by Fred Hutchinson Cancer Center: Statistical Analysis Plan: Statistical Analysis Plan  October 22, 2025Documents provided by Fred Hutchinson Cancer Center: Informed Consent Form  October 26, 2023