Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
Overview
- Phase
- Phase 3
- Status
- Terminated
- Enrollment
- 205
- Locations
- 20
- Primary Endpoint
- Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •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):
Arms & Interventions
IV Ganciclovir
5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge
Intervention: IV Ganciclovir (Drug)
Placebo
normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge
Intervention: Normal saline (Drug)
Outcomes
Primary Outcomes
Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure
Time Frame: up to 28 days
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 Outcomes
- 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)
- To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 7 days)
- To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups.(up to 28 days)
Investigators
Michael Boeckh
Professor, Vaccine and Infectious Disease Division, Fred Hutch
Fred Hutchinson Cancer Center