The goal of this prospective, interventional, single-center study is to assess whetherthe early detection of Influenza with smart wearable device algorithms and alerting,rapid testing, and subsequent Baloxavir treatment demonstrate better post-infectionoutcomes versus publicly available- and Centers for Disease Control (CDC)-derivednational statistics for equivalent household populations as well as pediatric kidney,heart, liver, lung transplant recipients and waitlisted patients.
Influenza infections are a significant concern for the clinical management of transplant
recipients, a highly vulnerable immunocompromised patient group. Early Influenza
detection has major benefits for the successful treatment in that crucial early infection
time window and allows for more timely mitigation measures to be employed. Xofluza®
(Baloxavir Marboxil), FDA approved in 2018 for the treatment of acute Influenza, has been
shown to have improved outcome characteristics versus Tamiflu® (Oseltamivir), as well as
compliance (a single pill given once, versus 10 pills taken over 5 days for Oseltamivir).
The timing of the influenza diagnoses and intervention greatly impacts the outcomes in
both antiviral medications though. Smart wearable devices have demonstrated clear utility
to detect early infection using physiological signatures such as sub-symptomatic
increases in heart rate (HR) and body temperature. Detection of Influenza and severe
acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been shown to be robustly
detectable several days prior to clinical symptoms onset in large well-powered smartwatch
studies.
This is a sub-study of the existing Institutional Review Board (IRB) # 20-017872
protocol: "Early Detection of SARS-CoV-2 & other Infections using Wearable Devices in
Pediatric Transplant Patients and Household Members". This is a prospective,
interventional, single-center study at The Children's Hospital of Philadelphia comprising
kidney, heart, liver and lung transplant recipients, waitlisted patients, and their
household members. Subjects will wear smart wearable devices to monitor biometrics
including HR, HR variation (HRV) and proxies of body temperature. A smart wearable device
alert generated from a validated early infection detection algorithm and alerting
platform, precipitates subjects to use an at-home collection kit for SARS-CoV-2,
Influenza A/B and respiratory syncytial virus (RSV) A/B which is then sent to a central
clinical lab for polymerase chain reaction (PCR)-based diagnoses. If the transplant
recipient is positive for Influenza A/B the local clinical care team will be informed to
determine if Baloxavir and/or any other medication is warranted. Genentech will make the
Baloxavir medication available via the CHOP transplant pharmacist through the recipients'
regular pharmacy. If the non-transplanted household members are positive for Influenza or
exposed to Influenza positive infected subject(s) their treatment will be determined by
their own primary-care. All CHOP transplant recipients will have their medical records
reviewed for relevant covariates and confounders after Baloxavir treatment. Study
subjects will complete short daily REDCap symptom forms for the pre-, peri- and
post-infection periods.
Drug: Baloxavir Marboxil
Baloxavir marboxil will be administered as either a tablet or granules. Dose is based on
body weight:
40 mg for a participants weighing 20-79 kg, or 80 mg for a patient weighing more than or
equal to 80 kg
Other Name: Xofluza
Inclusion Criteria
Population 1: Potential Baloxavir treatment group (CHOP transplant subjects 5 years & up)
- Willing CHOP male or female kidney, heart, liver or lung single or multiple
transplant recipients aged 5 years or older as per FDA guidelines.
- Willing to regularly wear a smartwatch and take an at-home positive respiratory
virus (RV) panel which will include a diagnoses of Influenza A or B.
- Have an antigen positive diagnoses of Influenza A or B (a PCR-based positive
clinical diagnoses of Influenza A or B may be requested in "alarm positive plus
antigen positive but asymptomatic" cases).
- Can be included if their treating physician prescribe prophylactic treatment of
Baloxavir if the subject has been exposed to Influenza.
- If Baloxavir is prescribed the study subject should be treated within 48 hours of
symptom onset (regardless of the alarming time).
Population 2: Potential Baloxavir treatment group (CHOP waitlisted subjects 5 years & up)
• Willing waitlisted CHOP kidney, heart, liver or lung single or multiple transplant
recipients aged 5 years or older, which are anticipated to have a transplant in the next
12 months.
Population 3: Potential Baloxavir treatment group (non-transplanted household members)
- Non-transplanted household member of a CHOP transplant recipient or waitlisted
patient
- Be at least 5 years of age.
- Willing to regularly wear a smartwatch and take an at-home positive respiratory
virus (RV) panel for diagnoses of Influenza A or B.
- Have a Antigen-based positive diagnoses of Influenza A or B
Population 4: Non-Baloxavir treatment subjects
- CHOP transplant recipients and all other non-transplanted household members who are
2-4 years of age.
- Subjects 5 years and up who are Influenza positive but whom do not receive Baloxavir
treatment
Exclusion Criteria
Population 1:
- Any allergy to Baloxavir (although they can remain in the study as an influenza case
or control without Baloxavir treatment, or if they have been treated with a
different medication for influenza) or a recommendation from the study
physicians'/transplant pharmacist(s) not to take Baloxavir.
- Subjects weighing < 20 kg
- If the subject is unable or unwilling to consent.
- If the subject is younger than 5 years of age.
- If the subject requires mechanical ventilation at time of enrollment.
- If the subject is pregnant or breast feeding at the time of early infection
alerting.
- If the subject is taking a prohibited medication. These include Influenza antiviral
drugs with the exception of oseltamivir and baloxavir (such as peramivir,
laninamivir, zanamivir, rimantadine, umifenovir or amantadine).
- Unwilling or unable to comply with the study requirements.
Population 2: All exclusion criteria listed for Population 1
Population 3:
- Subjects weighing < 20 kg
- A household transplant recipient is not participating in the study
- Any allergy to Baloxavir (although they will remain in the study as an influenza
case/control without treatment)
- A recommendation from the study physicians'/transplant pharmacist not to take
Baloxavir
- If the subject is unable or unwilling to consent.
- If the subject is younger than 5 years of age.
- If the subject is pregnant at screening.
- If the subject is taking a prohibited medication. These include Influenza antiviral
drugs with the exception of oseltamivir and baloxavir (such as peramivir,
laninamivir, zanamivir, rimantadine, umifenovir or amantadine).
- Unwilling or unable to comply with the study requirements.
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Investigator: Brendan Keating, PhD
Contact: 267-760-4507
bkeating@pennmedicine.upenn.edu
Brendan Keating, PhD
(267) 760-4507
bkeating@pennmedicine.upenn.edu
Mauricio Arcila-Mesa, MD
(267) 551-0862
arcilamesm@chop.edu
Matthew O Connor, MD, Principal Investigator
Children's Hospital of Philadelphia