Clinical trial NCT04712539: Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients
Official title: Efficacy of Combination Baloxovir and Oseltamivir Therapy in Influenza Infected Immunocompromised Hosts
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hematopoietic and Lymphoid Cell Neoplasm
Influenza
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2021-01-15
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.

Detailed description: PRIMARY OBJECTIVE:

I. To compare the efficacy of baloxavir marboxil (baloxavir) in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 1 from baseline for treatment of severe influenza infections in immunocompromised hosts (such as hematopoietic cell transplant \[HCT\] recipients and hematological malignancy \[HM\] patients) and compare the main clinical outcome, complicated hospital stay between the intervention arm and control arm.

SECONDARY OBJECTIVES:

I. To compare the efficacy of baloxavir in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 3, 7, 14 and 30 from baseline.

II. To measure the incidence of baloxavir and oseltamivir resistance, development of lower respiratory tract infections (LRTI), oxygen requirement, respiratory failure, changes in microbiome of the upper airway, length of hospital stay and all-cause mortality at day 30 while on baloxavir and/or oseltamivir in these immunocompromised hosts.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive oseltamivir orally (PO) twice daily (BID) for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up at 30 days.

Eligibility criteria: Inclusion criteria:

1. Hematopoeitic cell transplant recipients OR hematological malignancy patients
2. Diagnosed with influenza ⱡ
3. Evidence of LRTI\* or high risk upper respiratory tract infection (URTI)\*\*

ⱡ A positive multiplex PCR for influenza is required to confirm a diagnosis of influenza infection.

\* LRTI will be defined as influenza cases that have evidence of disease below the level of the trachea on either imaging only (possible LRTI), imaging and microbiological evidence of lower airway disease with a bronchoscopy (probable LRTD) or pathological evidence of disease via biopsy (proven LRTI).

\*\* High risk URI will be defined as those cases of influenza that do not have microbiological nor radiological evidence of LRTI, yet they have an immunodeficiency scoring index (ISI) of 3 or greater as defined by Shah D et al (19) for HCT recipients or severe neutropenia (ANC ≤500 cells/ml) and/or lymphopenia (ALC ≤200 cells/ml) for HM patients.

Exclusion criteria:

1. Patient requires mechanical ventilation at time of enrollment
2. Patient is younger than the age of 12 years old
3. The patient is unable to tolerate oral therapy
4. The patient is pregnant at screening ( Positive serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential).
5. The patient is on a prohibited medication. These include Influenza antiviral drugs with the exception of oseltamivir and baloxavir (such as peramivir, laninamivir, zanamivir, rimantadine, umifenovir or amantadine) and herbal therapies.
6. The patient is unable to consent will be excluded

Primary outcomes:
measure: Changes in viral loads
timeFrame: On day 0, 1, 3, 7, 14, and 30
measure: Incidence of complicated hospital stay
timeFrame: Up to 30 days
Secondary outcomes:
measure: Rate of resistance to antiviral agents
timeFrame: Up to 30 days
measure: Progression to lower respiratory tract infections
timeFrame: Up to 30 days
measure: Length of hospital stay
timeFrame: Up to 30 days
measure: Oxygen requirement
timeFrame: Up to 30 days
measure: Rate of respiratory failure
timeFrame: Up to 30 days
measure: 30-day mortality
timeFrame: At 30 days
measure: Changes in microbiome diversity
timeFrame: On day 0, 1, 3, 7, 14, and 30
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Roy F Chemaly, MD,MPH
role: PRINCIPAL_INVESTIGATOR
References: