Control of COVID-19 Outbreaks in Long Term Care

  • STATUS
    Recruiting
  • days left to enroll
    28
  • participants needed
    760
  • sponsor
    Appili Therapeutics Inc.
Updated on 26 January 2021
covid-19
post-exposure prophylaxis
favipiravir

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.

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.

Details
Condition *COVID-19, Covid-19, SARS-CoV-2, SARS-CoV-2, SARS-CoV-2, SARS-CoV-2, Sars Cov 2
Treatment Favipiravir, Favipiravir Placebo
Clinical Study IdentifierNCT04448119
SponsorAppili Therapeutics Inc.
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 65 yrs?
Gender: Male or Female
Do you have any of these conditions: Covid-19 or *COVID-19 or SARS-CoV-2?
Do you have any of these conditions: *COVID-19 or SARS-CoV-2 or Covid-19 or Sars Cov 2?
Inclusion criteria for LTCHs
LTCH in Ontario with >80% of residents being adults 65 years of age
Residents are or can be routinely assessed at least daily by staff
LTCH has not previously had a unit enrolled in this study
Outbreak of COVID-19 declared on at least one nursing unit, requiring all of the
following
2 to 4 residents who develop PCR-confirmed symptomatic COVID-19 infection on the same unit within 7 days at the time when the outbreak is identified as eligible
21 days from symptom onset in the index case at the time when the outbreak is identified as eligible
Cumulative attack rate in residents on the affected unit since the beginning of the pandemic 25% at the time when the outbreak is identified as eligible
20% of residents with microbiologically confirmed COVID-19 or line-listed as a presumptive case in a COVID-19 outbreak and not tested for COVID-19 in prior outbreaks within the last six months
Nursing unit with 16 and 32 residents
Nursing home agrees to work with study coordination to minimize the number of persons who provide care on the unit
Mechanism exists for delivery of medication and recording of administered medication for all residents
80% of residents on outbreak unit are eligible and they or their substitute decision makers consent to participate in the study
Written informed consent of Medical Director, Administrator and a delegate of the Residents' Council of the LTCH for LTCH to be included in the cluster trial
Inclusion criteria for LTCH residents
Informed consent from resident or substitute decision maker (SDM)
Inclusion criteria for LTCH staff
Expected to work at least two 8-hour shifts, or the equivalent time (16 hours on the unit) during the outbreak period
Informed consent

Exclusion Criteria

Exclusion criteria for LTCHs
Inability to deliver medication to consenting residents within 96 hours of identification of the outbreak
Inability to define a physically separate unit with 32 residents
Any of facility management, medical advisory committee or resident council do not approve participation
Exclusion criteria for LTCH Residents and Staff
Pregnancy (females < 55 years of age require a negative urine pregnancy test at enrollment, and either menopause or two concurrent reliable methods of contraception need to be confirmed)
History of abnormalities of uric acid metabolism, other than gout
History of hypersensitivity to remdesivir or favipiravir
Previous diagnosis of hepatic cirrhosis
Current use of the following medications, which cannot be discontinued for the duration of the study: pyrazinamide, hydralazine, more than 3000 mg of acetaminophen per day
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