COVID-19Phase 2NCT04448119
Control of COVID-19 Outbreaks in Long Term Care
A Phase 2 study testing Favipiravir in people with COVID-19 and SARS-CoV-2, run by Appili Therapeutics Inc. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- COVID-19, SARS-CoV-2
- What is being tested?
- Favipiravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteCanada
- Study dates
- 16 Oct 2020to 30 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Show all 16Show fewer
- 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.
- 1. Informed consent from resident or substitute decision maker (SDM)
- Expected to work at least two 8-hour shifts, or the equivalent time (16 hours on the unit) during the outbreak period.
- Informed consent.
Who cannot join
- 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.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Control of COVID-19 Outbreaks in Long Term Care (CONTROL-COVID)
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.
Read the 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
- Being tested
- Favipiravir, Favipiravir Placebo
- Keywords
- COVID-19, Long-Term Care Home, Favipiravir, Chemoprophylaxis, SARS-CoV-2
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FavipiravirDrug
Also called Avigan
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.
Favipiravir PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Chemoprophylaxis | Experimental | Participants of LTCH units allocated to the chemoprophylaxis arm receive favipiravir for 25 days. Residents in the LTCH unit diagnosed with COVID- 19 at enrollment will be offered treatment with favipiravir for 14 days. Receives: Drug: Favipiravir |
| Placebo | Placebo comparator | Participants of LTCH units allocated to the control arm receive placebo for 25 days. Residents in the LTCH unit diagnosed with COVID-19 at enrollment will be offered treatment with placebo for 14 days. Receives: Drug: Favipiravir Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Control of Outbreak
Control of outbreak, defined as no new cases of COVID-19 in residents for 24 consecutive days up to day 40 after the start of prophylaxis
Measured: Day 40
Secondary outcomes (9)
Mortality (Residents)
The proportion of residents of included LTCH units who die up to day 40, and up to day 60
Measured: Day 40, Day 60
COVID-19 Infection (Residents)
The proportion of residents of included LTCH units who were uninfected at baseline and develop new symptomatic microbiologically confirmed COVID-19 up to day 40
Measured: Day 40
COVID-19 Infection (Staff)
The proportion of exposed staff uninfected at baseline in whom SARS-CoV-2 infection is identified up to day 14 and up to day 40
Measured: Day 14, Day 40
Hospitalization (Residents)
The proportion of residents of included LTCH units hospitalized up to day 40
Measured: Day 40
Medication Discontinuation (Residents)
The proportion of residents of included LTCH units who discontinue study medication due to adverse events
Measured: Day 40
Medication Discontinuation (Staff)
The proportion of LTCH staff of included LTCH units who discontinue study medication due to adverse events
Measured: Day 40
COVID-19 in new LTCH Units (a)
The occurrence of new microbiologically confirmed COVID-19 infections in residents in other units of the LTCH up to day 40 (dichotomous, at LTCH level)
Measured: Day 40
COVID-19 in new LTCH Units (b)
The proportion of previously unaffected LTCH units of the remainder of the LTCH in which a case of COVID-19 is identified
Measured: Day 40
COVID-19 in new LTCH Units (c)
The proportion of residents in the remainder of the LTCH who develop COVID-19 infections up to day 40
Measured: Day 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start16 Oct 2020
- Primary completion30 Oct 2021
- Study completion30 Oct 2021
Why it stopped: Recruitment challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Appili Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MOUNT SINAI HOSPITAL, Applied Health Research Centre, Sunnybrook Health Sciences Centre, University Health Network, Toronto, University of Toronto
- Responsible party
- Sponsor
- Investigators
- Allison J McGeer, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04448119
- Sponsor's protocol ID
- CONTROL-COVID-Favipiravir-1
- Status last verified
- Feb 2023
- First submitted
- 24 Jun 2020
- Last updated
- 21 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Control of COVID-19 Outbreaks in Long Term Care (CONTROL-COVID)
- ClinicalTrials.gov ID
- NCT04448119
- Acronym / sponsor ID
- CONTROL-COVID-Favipiravir-1
- Conditions
- COVID-19, SARS-CoV-2
- Keywords
- COVID-19, Long-Term Care Home, Favipiravir, Chemoprophylaxis, SARS-CoV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment challenges
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Appili Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- MOUNT SINAI HOSPITAL, Applied Health Research Centre, Sunnybrook Health Sciences Centre, University Health Network, Toronto, University of Toronto
- Study start
- 16 Oct 2020 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Oct 2021 (actual)
- First posted
- 25 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chemoprophylaxis | Experimental | Drug: FavipiravirParticipants of LTCH units allocated to the chemoprophylaxis arm receive favipiravir for 25 days. Residents in the LTCH unit diagnosed with COVID- 19 at enrollment will be offered treatment with favipiravir for 14 days. |
| Placebo | Placebo comparator | Drug: Favipiravir PlaceboParticipants of LTCH units allocated to the control arm receive placebo for 25 days. Residents in the LTCH unit diagnosed with COVID-19 at enrollment will be offered treatment with placebo for 14 days. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (16 listed)
- 1. Informed consent from resident or substitute decision maker (SDM)
Key exclusion criteria (8 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FavipiravirAlso: AviganFavipiravir 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 | Chemoprophylaxis |
| Favipiravir PlaceboFavipiravir 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. | Drug | Placebo |
Primary outcome
Control of Outbreak
Time frame: Day 40
Control of outbreak, defined as no new cases of COVID-19 in residents for 24 consecutive days up to day 40 after the start of prophylaxis
9 secondary outcomes
Mortality (Residents)
Time frame: Day 40, Day 60
COVID-19 Infection (Residents)
Time frame: Day 40
COVID-19 Infection (Staff)
Time frame: Day 14, Day 40
Hospitalization (Residents)
Time frame: Day 40
Medication Discontinuation (Residents)
Time frame: Day 40
Medication Discontinuation (Staff)
Time frame: Day 40
COVID-19 in new LTCH Units (a)
Time frame: Day 40
COVID-19 in new LTCH Units (b)
Time frame: Day 40
COVID-19 in new LTCH Units (c)
Time frame: Day 40
Results and safety
The study was stopped early (reason given: Recruitment challenges). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allison J McGeer, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Favipiravir in people with COVID-19 and SARS-CoV-2, run by Appili Therapeutics Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment challenges). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Control of Outbreak (time frame: Day 40). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.