COmbination Therapy With Baloxavir and Oseltamivir 1 for Hospitalized Patients With Influenza (The COMBO Trial 1)

NCT ID: NCT04327791

Last Updated: 2023-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-03

Study Completion Date

2025-06-01

Brief Summary

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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).

Detailed Description

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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).

* Group 1, the combination treatment group will receive oseltamivir and baloxavir

* Oseltamivir: 75 mg po bid for 5 days
* Baloxavir: 40 mg po once for wt \< 80 kg OR 80 mg po once for wt \>/= 80 kg
* Group 2, the standard treatment group will receive oseltamivir and placebo

* Oseltamivir: 75 mg po bid for 5 days
* Placebo: Once

Oseltamivir dosing may be reduced for patients with decreased renal function as follows, per treating physician:

* CrCl \> 60 mL/minute: No dosage adjustment
* CrCl \> 30 to 60 mL/minute: 30 mg po bid
* CrCl \> 10 to 30 mL/minute: 30 mg po qd
* HD: 30 mg po once and 30 mg po after each HD session
* CAPD: 30 mg po once
* 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 Data Monitoring Committee (DMC) quarterly and as needed throughout the trial.

Conditions

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Influenza

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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baloxavir

Baloxavir: 40 mg po once for wt \< 80 kg OR 80 mg po once for wt \>/= 80 kg

Group Type EXPERIMENTAL

Baloxavir

Intervention Type DRUG

administered PO once

placebo

placebo po once

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

administered PO once

Interventions

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Baloxavir

administered PO once

Intervention Type DRUG

Placebos

administered PO once

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Adults \>/= 18 years old
2. Laboratory confirmed influenza A and/or B (rapid test or PCR)
3. 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
4. Oseltamivir treatment ordered by clinical team AND patient is able to be enrolled:

* Prior to the initial dose of oseltamivir OR
* Within 60 minutes after the initial dose of oseltamivir
5. Subject or Legally Authorized Representative able to and willing to provide written informed consent
6. Able to commit to 30 days of follow up
7. Weight \> 40 kg
8. SARS-CoV-2 PCR swab sent within 1 week of enrollment

Exclusion Criteria

1. ESRD not undergoing hemodialysis (HD) or peritoneal dialysis (CAPD)
2. Severe hepatic insufficiency, cirrhosis, acute or chronic liver failure
3. Nausea/vomiting, aspiration risk, or other conditions precluding the ability to use oral medications (if patient is NPO including meds, otherwise unable to swallow oral medications)
4. Influenza medication use within the prior week, other than the initial oseltamivir given during this hospitalization for this episode of influenza
5. Oseltamivir or baloxavir allergy or intolerance
6. Pregnancy (need negative pregnancy test (urine or blood) in reproductive age women)
7. Absence of dependable contraception in reproductive age women
8. Inability to obtain informed consent
9. Refusal of oseltamivir therapy by patient as baseline treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Viroclinics Biosciences B.V.

INDUSTRY

Sponsor Role collaborator

Bassett Healthcare

OTHER

Sponsor Role lead

Responsible Party

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Daniel Freilich, MD

attending physician - hospitalist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daniel Freilich, MD

Role: PRINCIPAL_INVESTIGATOR

Bassett Medical Center

Locations

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Baystate Medical Center

Springfield, Massachusetts, United States

Site Status RECRUITING

Bassett Medical Center

Cooperstown, New York, United States

Site Status RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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jennifer Victory, RN

Role: CONTACT

6075476965

Daniel Freilich, MD

Role: CONTACT

6075474586

Facility Contacts

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Andres Santana

Role: primary

413-794-4231

jennifer Victory, RN

Role: primary

607-547-6965

Jose Pena

Role: primary

503-494-2736

Other Identifiers

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1579493

Identifier Type: -

Identifier Source: org_study_id

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