COMBO 1: COmbination Therapy With Baloxavir and Oseltamivir 1 for Hospitalized Patients With Influenza (The COMBO Trial 1)
Study Details
Study Description
Brief Summary
This is a randomized, double-blind, placebo-controlled Phase 2-like, investigator-directed trial of hospitalized patients with laboratory confirmed influenza. Eligible and consented patients will be randomly assigned, in a 1:1 ratio, to one of two groups: Group 1, the combination treatment group (oseltamivir and baloxavir); Group 2, the standard treatment group (oseltamivir and placebo).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Up to 60 hospitalized patients with laboratory confirmed influenza who provide informed consent and meet trial inclusion/exclusion criteria.
Experimental Design and Methods In a randomized, double-blind, placebo-controlled Phase 2-like, investigator-directed trial, hospitalized patients with laboratory confirmed influenza meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and enrolled randomly in a 1:1 ratio to one of two groups upon signing of the study's informed consent form: Group 1, the combination treatment group (oseltamivir and baloxavir); Group 2, the standard treatment group (oseltamivir and placebo).
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Group 1, the combination treatment group will receive oseltamivir and baloxavir
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Oseltamivir: 75 mg po bid for 5 days
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Baloxavir: 40 mg po once for wt < 80 kg OR 80 mg po once for wt >/= 80 kg
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Group 2, the standard treatment group will receive oseltamivir and placebo
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Oseltamivir: 75 mg po bid for 5 days
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Placebo: Once
Oseltamivir dosing may be reduced for patients with decreased renal function as follows, per treating physician:
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CrCl > 60 mL/minute: No dosage adjustment
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CrCl > 30 to 60 mL/minute: 30 mg po bid
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CrCl > 10 to 30 mL/minute: 30 mg po qd
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HD: 30 mg po once and 30 mg po after each HD session
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CAPD: 30 mg po once
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CRRT: 30 mg po qd After assignment of a unique study number after signing informed consent, baseline data will be collected at time 0 including personal and clinical information and protocol directed laboratory specimens - nasal swabs for influenza PCR for patients who only had a rapid antigen test and blood specimens for patients who consent to additional blood drawing (for improved efficacy and safety analyses; not required for enrollment). Patients will be given oseltamivir by their healthcare providers. Research personnel's only involvement for oseltamivir dosing will be to remind providers that earlier treatment improves efficacy. Patients will then be given a single dose of baloxavir or placebo by the study's CRC as per a computerized random allocation scheme with dose determined by weight (as above); the CRC will notify the patient's provider that the patient has been given the single (blinded) dose. At time 1, 2, 3, 4, 7, and 30 days, nasal swabs will again be obtained, clinical information will be obtained from the patient via interview and review of the EMR, and blood specimens for patients who consented to additional blood drawing. Follow up will continue for 30 days.
Efficacy and adjudicated safety data points will be assessed by a blinded Data Monitoring Committee (DMC) after completion of the trial.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: baloxavir Baloxavir: 40 mg po once for wt < 80 kg OR 80 mg po once for wt >/= 80 kg |
Drug: Baloxavir
administered PO once
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| Placebo Comparator: placebo placebo po once |
Drug: Placebos
administered PO once
|
Outcome Measures
Primary Outcome Measures
- Time to Clearance of Viral Shedding [30 days]
influenza viral titer obtained by nasal swab using qCulture
Eligibility Criteria
Criteria
Inclusion Criteria
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Adults >/= 18 years old
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Laboratory confirmed influenza A and/or B (rapid test or PCR)
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Able to be enrolled, randomized, and dosed with study drug within 8 hours of the decision to admit patient to hospital for treatment of influenza
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Oseltamivir treatment ordered or started by clinical team
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Able to and provide written informed consent
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Able to commit to 30 days of follow up
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Weight > 40 kg
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SARS-CoV-2 PCR swab sent within 1 week of enrollment
Exclusion Criteria
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ESRD not undergoing hemodialysis (HD) or peritoneal dialysis (CAPD)
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Severe hepatic insufficiency, cirrhosis, acute or chronic liver failure
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Nausea/vomiting, aspiration risk, or other conditions precluding the ability to use oral medications (if patient is NPO including meds) unless gastric tube use available (e.g., NG tube, G tube, etc.)
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Influenza medication use within the prior week, other than the initial oseltamivir given during this hospitalization for this episode of influenza
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Oseltamivir or baloxavir allergy or intolerance
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Pregnancy (need negative pregnancy test (urine or blood) in reproductive age women)
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Absence of dependable contraception in reproductive age women
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Inability to obtain informed consent
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Refusal of oseltamivir therapy by patient as baseline treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bassett Medical Center | Cooperstown | New York | United States | 13326 |
Sponsors and Collaborators
- Bassett Healthcare
- Genentech, Inc.
- Viroclinics Biosciences B.V.
Investigators
- Principal Investigator: Daniel Freilich, MD, Bassett Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1579493