Adaptive Platform Trial of Treatments for Respiratory Infections in Community Settings (TreatResp)

Unity Health Toronto

Status and phase: Not yet enrolling; Phase 3

Conditions: Influenza A; Acute Respiratory Infections (ARIs); SAR-CoV-2; Influenza B

Treatments: Drug: Placebo Control; Drug: Baloxavir

Study type: Interventional

Funder types: Other

Identifiers

NCT07314905

CTO 5178

Details and patient eligibility

About

TreatResp is a double-blind, individually randomized, multi-centre adaptive platform trial. TreatResp aims to establish an adaptive platform trial aimed at evaluating the clinical- and cost-effectiveness, practical challenges, and outcomes of therapeutics for respiratory pathogens in non-hospitalized patients. Participants will be randomized to receive usual care (i.e., supportive care and symptom relief) or a study therapeutic, which will be determined by the TreatResp Therapeutics Committee. The primary outcomes being evaluated is time to recovery.

Full description

Effective and affordable therapeutics for respiratory pathogens that can be used easily in community settings are needed to accelerate recovery, prevent hospitalizations and deaths. The Adaptive Platform Trial of Treatments for Respiratory Infections in Community Settings (TreatResp) will evaluate the clinical effectiveness and cost-effectiveness of therapeutics for respiratory pathogens in non-hospitalized patients. Adaptive platform trials (APTs) are designed to compare multiple therapies in an efficient manner and allow us to respond to the dynamic nature of pandemics. Therapeutics to be evaluated will be identified through a transparent TreatResp Therapeutics Committee. The primary outcome is time to recovery (defined as the first instance that a participant report feeling fully recovered), and key secondary outcomes include all-cause emergency department (ED) visit and/or hospitalization and/or death at 28 days, time to sustained resolution, time to progression of signs or symptoms, symptom severity, quality of life, and cost-effectiveness of each therapeutic. TreatResp leverages our CBRF funded Pandemic Preparedness Engaging Primary Care and Emergency Departments (PREPARED) initiative to recruit participants to the study.

Enrollment: 264 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years or older

• A positive test (PCR or RAT) for one of the pathogens included in the trial's domains (influenza A/B, or other future specified respiratory pathogens),

• Enrolled within 5 days of symptoms onset. However, this window may vary depending on the domain or specific interventions within each domain (for example 72 hours for Baloxavir).

• At least two symptoms commonly associated with respiratory infections, including:

  • rhinitis
  • cough
  • wheezing
  • sore throat
  • nasal congestion
  • shortness of breath
  • fatigue
  • rapid breathing
  • excessive mucus production
  • loss of smell or taste
  • hemoptysis
  • trouble sleeping or insomnia due to breathing difficulties
  • fever (defined for purposes of this study as >37.5°C/ 41).

Exclusion criteria

• Admitted to hospital or in an ED for more than 24 hours
• Previously randomized to TreatResp within the past 12 months
• Currently participating in a clinical trial of a therapeutic agent for acute respiratory pathogen infection that is not/suspected not compatible with the study therapeutics
• Already taking a study therapeutic or contraindication to a study therapeutic
• Inability for participant or caregiver to provide informed consent.

Additional eligibility criteria will be applied based on the intervention assigned. For instance, if a participant is randomized to an antiviral treatment, they must not have contraindications specific to that antiviral. This ensures that each treatment is evaluated in a population for whom it is most appropriate and safe.

Baloxavir exclusion:

• Has a known or suspected pregnancy
• Is breastfeeding
• Is of childbearing potential and is not willing to use a highly effective contraceptive
• Has advanced chronic kidney disease (CKD stage 3: eGFR ≥30 to <60 mL/min, and severe renal impairment (eGFR <30 ml/min, CKD stage 4-5)
• Has severe hepatic impairment, or requires a live viral vaccine within the next seven days
• Has a significant impaired immunity (e.g., due to long-term oral steroids, chemotherapy, or an immune disorder)
• Requires immediate antiviral treatment or hospitalization as per the clinician's judgment
• Is allergic to trial medications
• Is scheduled for elective surgery or procedures requiring general anesthesia within the next two weeks
• Is co-infected with viruses of interest
• Received a live viral vaccine within the last 14 days

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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264 participants in 2 patient groups, including a placebo group

Acute Influenza A/B - Matched placebo for Baloxavir

Placebo Comparator group

Description:

Usual Care (i.e., supportive care and symptom relief). Matching control placebo for Baloxavir - a single matching dose.

Treatment:

Drug: Placebo Control

Acute Influenza A/B - Baloxavir

Experimental group

Description:

The adaptative platform trial will assess therapeutics for influenza A/B in out-patient setting. Interventions include: Baloxavir. Baloxavir dose: if weight \<80 kg: one 40 mg dose for 1 day; if weight ≥80kg, one 80 mg dose for one day.

Treatment:

Drug: Baloxavir