Acute Respiratory FailurePhase 3GRAIL^3NCT04706507
Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
A Phase 3 study testing IV Ganciclovir and Normal saline in people with Acute Respiratory Failure, run by Fred Hutchinson Cancer Center at 20 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Respiratory Failure
- What is being tested?
- IV Ganciclovir and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 205 participants
- Where
- 20 sitesUnited States
- Study dates
- 29 Jun 2021to 8 Apr 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48109-5360
Johns Hopkins University
Baltimore, Maryland, 21218
Brigham & Women's Hospital
Boston, Massachusetts, 02115
University of Vermont College of Medicine
Burlington, Vermont, 05405
Medical College of South Carolina
Charleston, South Carolina, 29425
University of Cincinnati
Cincinnati, Ohio, 45221
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University Medical Center
Columbus, Ohio, 43210
University of Colorado Denver
Denver, Colorado, 80204
Henry Ford Hospital
Detroit, Michigan, 48202
Duke University
Durham, North Carolina, 27708
University of Wisconsin School of Medicine & Public Health
Madison, Wisconsin, 53792
Intermountain Medical Center
Murray, Utah, 84107
Vanderbilt University
Nashville, Tennessee, 37235
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
Harborview Medical Center
Seattle, Washington, 98104
University of Washington Medical Center
Seattle, Washington, 98195
Washington University
St Louis, Missouri, 63130
Montefioure Medical Center
The Bronx, New York, 10467
Wakeforest University, School of Medicine
Winston-Salem, North Carolina, 27157
About this study
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
- Being tested
- IV Ganciclovir, Normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV GanciclovirDrug
Also called Cytovene
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.
Normal salineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| IV Ganciclovir | Experimental | 5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge Receives: 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 Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 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.
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.
Measured: 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.
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).
Measured: 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.
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.
Measured: 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.
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.
Measured: up to 28 days
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.
Measured: up to 7 days
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2021
- Study start29 Jun 2021
- Primary completion25 Oct 2024
- Study completion8 Apr 2025
Why it stopped: due to increased mortality and futility analyses
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Michael Boeckh, Fred Hutchinson Cancer Center
- Investigators
- Michael Boeckh, MD, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04706507
- Sponsor's protocol ID
- RG1121219
- Other IDs
- 1UG3HL147011-01A1, 10547
- Acronym
- GRAIL^3
- Status last verified
- Nov 2025
- First submitted
- 23 Dec 2020
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
- ClinicalTrials.gov ID
- NCT04706507
- Acronym / sponsor ID
- GRAIL^3 / RG1121219
- Conditions
- Acute Respiratory Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to increased mortality and futility analyses
- Enrolment
- 205 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 29 Jun 2021 (actual)
- Primary completion
- 25 Oct 2024 (actual)
- Study completion
- 8 Apr 2025 (actual)
- First posted
- 12 Jan 2021 (actual)
- Results
- Posted 12 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Ganciclovir | Experimental | Drug: IV Ganciclovir5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge |
| Placebo | Placebo comparator | Drug: Normal salinenormal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (22 listed)
- Known or suspected immunosuppression, including:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV GanciclovirAlso: CytoveneFor 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. | Drug | IV Ganciclovir |
| Normal salineFor 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. | Drug | Placebo |
Primary outcome
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.
10 secondary outcomes
To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: up to 28 days
To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
Time frame: up to 7 days
To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients.
Time frame: 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.
Time frame: 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.
Time frame: up to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Boeckh, MD principal investigator
Fred Hutchinson Cancer Center
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IV Ganciclovir and Normal saline in people with Acute Respiratory Failure, run by Fred Hutchinson Cancer Center at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure (time frame: up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.