Ganciclovir for Acute Respiratory Failure

(GRAIL^3 Trial)

Recruiting at 19 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

500 Participants Needed

Trial Summary

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 ganciclovir generally safe for humans?

Ganciclovir has been used to treat various conditions, and while it can be effective, it may cause side effects like neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and kidney issues. However, in some studies, no severe drug-related toxicities were observed, indicating it can be safe under certain conditions. ^{1 2 3 4 5}

How is the drug Ganciclovir unique for treating acute respiratory failure?

Ganciclovir is unique for treating acute respiratory failure because it is an antiviral medication typically used for viral infections, which may be relevant if the respiratory failure is caused by a virus, especially in immunocompromised patients. This approach differs from standard treatments like noninvasive ventilation, which focus on supporting breathing rather than addressing viral causes. ^{6 7 8 9 10}

What is the purpose of this trial?

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

Research Team

Michael Boeckh, MD

Principal Investigator

Fred Hutchinson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of ganciclovir for cytomegalovirus disease. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Risk factors for ganciclovir-induced thrombocytopenia and leukopenia. [2015]

3. Denmark pubmed.ncbi.nlm.nih.gov

Safety and efficacy of prolonged cytomegalovirus prophylaxis with intravenous ganciclovir in pediatric and young adult lung transplant recipients. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Ganciclovir treatment of serious cytomegalovirus infection in heart and heart-lung transplant recipients. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of cytomegalovirus retinitis with ganciclovir. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Non-invasive ventilation in immunosuppressed patients with pneumonia and extrapulmonary sepsis. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Prognosis of critically ill immunocompromised patients with virus-detected acute respiratory failure. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Noninvasive ventilation for patients presenting with acute respiratory failure: the randomized controlled trials. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Early non-invasive ventilation for acute respiratory failure in immunocompromised patients (IVNIctus): study protocol for a multicenter randomized controlled trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Use of noninvasive ventilation in immunocompromised patients with acute respiratory failure: a systematic review and meta-analysis. [2018]