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

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 sourceof acute respiratory failure (Respiratory failure associated with infection confersat least 2 SOFA points above assumed baseline SOFA score of 0, thereby meetingSepsis-3 definition).

Exclusion Criteria:

• Known or suspected immunosuppression, including:

• HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; anegative HIV test is not required for enrollment)

• stem cell transplantation:

• within 6 months after autologous transplantation or

• within 1 years after allogeneic transplantation (regardless ofimmunosuppression)

• greater than 1 year of allogeneic transplantation if still taking systemicimmunosuppression or prophylactic antibiotics (e.g. for chronic graftversus host disease) Note: if details of stem cell transplantation areunknown, patients who do not take systemic immunosuppression and do nottake anti-infective prophylaxis are acceptable for enrollment andrandomization.

• solid organ transplantation with receipt of systemic immunosuppression (anytime)

• 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 (seeAppendix C):

• within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies, orother immunosuppressive drugs associated with CMV reactivation Note: if noinformation on these agents is available in the history and no direct orindirect evidence exists from the history that any condition exists thatrequires treatment with these agents (based on the investigator'sassessment), the subject may be enrolled. For all drug information,next-of-kin estimates are acceptable. See Appendix C for commonlyprescribed immunosuppressive agents. Information on the use of biologicswith moderate immunosuppressive effect but no known effect on CMV arepermitted 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 chroniccare ward, such as a rehabilitation unit, with an acute event are acceptable).

• Pregnant or breastfeeding (either currently or expected within one month). Note: forwomen of childbearing age (18-60 years, unless documentation of surgicalsterilization [hysterectomy, tubal ligation, oophorectomy]), if a pregnancy test hasnot been done as part of initial ICU admission work-up, it will be ordered stat anddocumented to be negative before randomization. Both urine and blood tests areacceptable.

• 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 therapeuticagent known or suspected to have anti-CMV activity or to be associated withsignificant 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