Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

Influenza Clinical Trial

Official title:

Efficacy of Combination Baloxovir and Oseltamivir Therapy in Influenza Infected Immunocompromised Hosts

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04712539
• Other study ID #: 2020-0919
• Secondary ID: NCI-2020-1391820
• Status: Recruiting
• Phase: Phase 2
• Start date: October 11, 2021
• Est. completion date: February 28, 2028

Study information

• Verified date: February 2024
• Source: M.D. Anderson Cancer Center
• Contact: Roy F. Chemaly, MD,MPH
• Phone: 713-792-6830
• Email: rfchemaly[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 28, 2028
• Est. primary completion date: February 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion criteria:

1. Hematopoeitic cell transplant recipients OR hematological malignancy patients

2. Diagnosed with influenza ?

3. Evidence of LRTI* or high risk upper respiratory tract infection (URTI)**

? 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 ß-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

Related Conditions & MeSH terms

• Hematopoietic and Lymphoid Cell Neoplasm
• Influenza
• Influenza, Human

Intervention

Drug:
• Baloxavir Marboxil
Given PO
• Oseltamivir
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in viral loads	Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.	On day 0, 1, 3, 7, 14, and 30
Primary	Incidence of complicated hospital stay	Defined as a hospital admission that was either prolonged (greater than 7 days), requiring intensive care unit level of care or death at day 30 as a result of influenza infection.	Up to 30 days
Secondary	Rate of resistance to antiviral agents	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Secondary	Progression to lower respiratory tract infections	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Secondary	Length of hospital stay	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Secondary	Oxygen requirement	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Secondary	Rate of respiratory failure	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Secondary	30-day mortality	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	At 30 days
Secondary	Changes in microbiome diversity	Analysis of alpha and beta diversity of microbiome will be assessed using Agile Toolkit for Incisive Microbial Analyses. Using Shannon index, we will quantify the alpha diversity of the microbiome. Changes in microbiome diversity will be made by comparing alpha diversity at each time point of sample collection (days 0, 1, 3, 7, 14 and 30).	On day 0, 1, 3, 7, 14, and 30

External Links

•   MD Anderson Cancer Center