NCT04448119

Control of COVID-19 Outbreaks in Long Term Care

Control of COVID-19 Outbreaks in Long Term Care (CONTROL-COVID)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Appili Therapeutics Inc. · Industry
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

To address the need to intervene to prevent the spread of COVID-19 in long-term care homes, we propose a randomized clinical trial of chemoprophylaxis in long-term care homes experiencing COVID-19 outbreaks. LTCH units experiencing an outbreak of COVID-19 will be randomized to chemoprophylaxis with favipiravir or placebo in a 1:1 ratio. Chemoprophylaxis in this setting refers to the use of favipiravir for pre-exposure prophylaxis, post-exposure prophylaxis, pre-emptive therapy, or treatment for established COVID-19. This design mimics the approach to influenza outbreaks, which has proven efficacy for outbreak control. The primary outcome will be control of the outbreak, defined as no new microbiologically confirmed case of COVID-19 for 24 consecutive days up to day 40.

Detailed description

Early in the COVID-19 pandemic, it became apparent that the elderly are disproportionately bearing the burden of disease and mortality. Many outbreaks are occurring in long-term care homes (LTCHs), with strikingly high mortality rates: nearly two-thirds of all Canadian COVID- 19 deaths are in LTCH residents. This is unsurprising, as viral respiratory outbreaks in LTCHs are devastating: before the use of influenza vaccine, case fatality rates during influenza outbreaks were as high as 55%. Interventions are thus urgently needed to control LTCH outbreaks to mitigate harms to this vulnerable population and maximize acute care capacity. Chemoprophylaxis is the cornerstone of management of LTCH influenza outbreaks and disease prophylaxis has been deemed a critical COVID-19 research priority by the World Health Organization. While definitive therapies do not yet exist, there is significant interest in repurposing existing anti-viral agents against COVID-19. Favipiravir, a broad spectrum antiviral agent, demonstrates activity against SARS-CoV-2 in vitro, and was associated with faster viral clearance, radiographic improvement, and clinical recovery in early trials. Favipiravir is an ideal candidates for chemoprophylaxis, as it is orally available and has a reasonable safety profile. To address the need to intervene to prevent the spread of COVID-19 in LTCHs, we propose a cluster-randomized placebo-controlled trial of chemoprophylaxis in LTCHs experiencing COVID-19 outbreaks. This study is a partially blinded, placebo-controlled cluster randomized trial of chemoprophylaxis to control outbreaks of COVID-19 in LCTHs for the elderly. The unit of analysis is a ward/unit. An outbreak is defined as ≥ 2 symptomatic microbiologically-confirmedCOVID-19 cases within 7 days on the LTCH unit. This design is selected to mimic the current approach to outbreaks of other respiratory viral infections, both because this approach has proven effective for these other viruses, and because it is standard practice and therefore feasible to implement. Eligible LTCHs will be asked to report outbreaks to the study in addition to the legally-required reporting to their local public health unit; public health units will also be asked to discuss the study with LTCHs reporting outbreaks. In addition, study staff will contact the infection control practitioner in each of the screened LTCHs twice weekly, to ensure the prompt identification of outbreak units. Residents and staff will be assessed for contraindications to enrollment and informed consent will be obtained for residents and staff to receive the allocated intervention, and to be followed up individually for clinical outcomes, adherence and safety during the outbreak. LTCH units experiencing an outbreak of COVID-19 will be randomized to either favipiravir or placebo in a 1:1 ratio. Favipiravir or placebo will be offered to all residents and staff who will be working on the unit during the chemoprophylaxis period, according to the allocation. Study drug will continue for a duration of 25 days. The dosage for favipiravir to be used in this study for chemoprophylaxis is 1600 mg (8 x 200 mg tablets) orally twice daily on day 1 followed by 800 mg (4 x 200 mg tablets) orally twice daily on day 2-25. Residents in the LTCH unit diagnosed with COVID-19 at enrollment will be offered treatment with favipiravir or placebo for 14 days, according to the LTCH unit allocation. The dose of favipiravir for treatment is 2000mmg orally twice daily on day 1, then 1000 mg orally twice daily for 13 additional days. Surveillance for infection will occur as usual for resident illness within each LTCH; staff will be asked to report symptoms and will be screened for symptoms each time they enter the building. Consenting residents and staff will be screened at day 0, day 14 and day 40 to identify asymptomatic infections and to assess duration of viral shedding. The primary outcome will be control of the outbreak, defined as no new microbiologically confirmed case of COVID-19 for 24 consecutive days up to day 40.

Conditions

• COVID-19
• SARS-CoV-2

Interventions

Type	Name	Description
DRUG	Favipiravir	Favipiravir is the experimental drug. The dosage for favipiravir to be used in this study for prophylaxis is 1600 mg (8 x 200 mg tablets) orally twice daily on day 1 followed by 800 mg (4 x 200 mg tablets) orally twice daily on days 2-25. The dose of favipiravir for treatment is 2000 mg orally twice daily on day 1, the 1000 mg orally twice daily for 13 additional days.
DRUG	Favipiravir Placebo	Favipiravir Placebo is the placebo drug. For chemoprophylaxis, the dosage of favipiravir placebo is 8 tablets orally twice daily on day 1, followed by 4 tablets twice daily from days 2-25. The dosage of favipiravir placebo for treatment is 10 tablets orally twice daily on day 1, followed by tablets twice daily from days 2-14.

Timeline

• Start date: 2020-10-16
• Primary completion: 2021-10-30
• Completion: 2021-10-30
• First posted: 2020-06-25
• Last updated: 2023-02-21

Locations

1 site across 1 country: Canada