Ganciclovir for Acute Respiratory Failure

(GRAIL^3 Trial)

Not currently recruiting at 21 trial locations

Overseen By Louise Kimball, PhD,RN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Anti-CMV drugs

Disqualifiers: Immunosuppression, Pregnancy, Cirrhosis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to hospital discharge

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ganciclovir, an antiviral medication, can help people with sepsis-related acute respiratory failure breathe easier and reduce time on ventilators. The researchers aim to determine if early administration of ganciclovir can prevent the reactivation of the CMV virus, which may worsen the condition. Participants will receive either ganciclovir or a placebo to compare outcomes. Suitable candidates are adults in the ICU with respiratory failure due to infection and a history of CMV exposure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used anti-CMV drugs like ganciclovir within seven days before joining the trial.

Is there any evidence suggesting that ganciclovir is likely to be safe for humans?

Previous studies have tested ganciclovir for safety in patients with conditions similar to those in this trial. Research shows that the main safety concerns include bone marrow damage and sudden kidney problems, observed in a small number of patients. However, not everyone experiences these side effects.

Ganciclovir is already used in other medical situations, suggesting it is generally well-tolerated under medical supervision. Prospective participants should discuss potential risks with a healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ganciclovir is unique because it offers a targeted antiviral approach to treating acute respiratory failure. Most current treatments for respiratory failure, such as mechanical ventilation and supportive care, focus on managing symptoms rather than directly attacking the underlying viral causes. Ganciclovir specifically targets viral replication, which could potentially reduce the severity and duration of the condition. Researchers are excited about this treatment because it opens up the possibility for more effective management of viral-induced respiratory failure, potentially leading to quicker recovery times and reduced hospital stays.

What evidence suggests that ganciclovir might be an effective treatment for acute respiratory failure?

Research has shown that ganciclovir can help prevent the reactivation of cytomegalovirus (CMV) in patients with severe lung issues due to sepsis. Studies have found that this can lead to better health outcomes, such as more days without needing a ventilator. Evidence also suggests that ganciclovir lowers inflammation markers, like IL-6, which are often elevated in these cases. In this trial, some participants will receive ganciclovir, while others will receive a placebo. Patients who received ganciclovir in previous studies generally fared better than those who did not, indicating its potential usefulness in critical care. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael Boeckh, MD

Principal Investigator

Fred Hutchinson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 in ICU with sepsis-associated acute respiratory failure who are CMV seropositive and expected to need respiratory support for at least two more days. Excluded are those with organ transplants, certain immunodeficiencies, severe neutropenia, allergies to ganciclovir, recent chemotherapy, advanced liver disease, or on other investigational anti-CMV drugs.

Inclusion Criteria

I have an infection causing severe breathing problems.

I have tested positive for CMV antibodies.

I will need help with breathing for at least 2 more days.

Exclusion Criteria

Pregnant or breastfeeding (either currently or expected within one month)

I was born with an immune deficiency and need medicine to prevent infections.

I haven't taken anti-CMV drugs in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive IV ganciclovir or placebo for 5 days, followed by once daily administration until hospital discharge

Up to hospital discharge

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ganciclovir

Trial Overview The study tests if IV Ganciclovir can increase ventilator-free days in patients with sepsis-induced acute respiratory failure by preventing CMV reactivation. It's a phase 3 trial hypothesizing that early treatment leads to better outcomes.

How Is the Trial Designed?

Group I: IV Ganciclovir Experimental Treatment 1 Intervention

5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge

Group II: Placebo Placebo Group 1 Intervention

normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04706507

Study Details | NCT04706507 | Ganciclovir to Prevent ... To evaluate whether administration of ganciclovir increases ventilator-free days in immunocompetent patients with sepsis-associated acute respiratory failure.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12323660/

Efficacy and toxicity analysis of ganciclovir in patients with ... As regards clinical efficacy, the treatment efficacy was defined by an increase or decrease in CMV CT, whereas a decrease indicated treatment failure. For ...

3. hopkinsmedicine.org hopkinsmedicine.org/clinical-trials/results/irb00279730

Ganciclovir to Prevent Reactivation of Cytomegalovirus in ... ... effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory failure thereby leading to improved clinical outcomes.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5817487/

Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus ... ... respiratory failure, including those with acute respiratory distress syndrome (ARDS). ... efficacy measure in clinical trials of treatments for acute respiratory ...

5. annalsofintensivecare.springeropen.com annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00793-2

Preemptive ganciclovir for mechanically ventilated patients ... The main safety endpoints were myelotoxicity and acute renal failure. Data safety monitoring board. Safety oversight was under the direction ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7876264/

Preemptive ganciclovir for mechanically ventilated patients ... The main safety endpoints were myelotoxicity and acute renal failure. ... Acute respiratory failure, 13 (35.1), 12 (30.8). Septic shock, 8 (21.6) ...

7. healio.com healio.com/news/pulmonology/20250605/ganciclovir-prophylaxis-shows-no-respiratory-supportfree-day-mortality-benefit-in-sepsis

Ganciclovir prophylaxis shows no respiratory support-free ... Ganciclovir to prevent reactivation of cytomegalovirus in patients with sepsis-associated acute respiratory failure: A phase 3 randomized ...