Overview

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

Status:
Recruiting
Trial end date:
2027-08-31
Target enrollment:
0
Participant gender:
All
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
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Fred Hutchinson Cancer Research Center
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Treatments:
Ganciclovir
Ganciclovir triphosphate
Criteria
Inclusion Criteria:

- Subject/next of kin informed consent

- Age > 18 years

- CMV IgG seropositive by standard serologic methods

- Intubated and requiring mechanical positive pressure ventilation with positive
end-expiratory pressure (PEEP) > 5 cmH2O; PaO2/FiO2 < 300mmHg; and new, or if no prior
imaging, presumed new unilateral or bilateral infiltrates on chest radiography
occurring in the setting of sepsis from any source

- Meets criteria for sepsis within a 24-hour time period within the 120-hour screening
window after hospitalization). Sepsis will be defined according to the recent Sepsis-3
consensus definition (outlined briefly below and in more detail in Appendix G) [70]:

- Infection suspected or confirmed by the treating physician and

- Organ dysfunction measured as an acute change in total SOFA score >2 points after
the infection (baseline SOFA score assumed 0 unless known pre-existing organ
dysfunction).

- On the day of randomization (by local criteria):

- Not eligible for SBT (Spontaneous Breathing Trial. Use of sedation and/or
vasopressor does not specifically contraindicate SBT) Or

- Failed SBT

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