The Containing Coronavirus Disease 19 (COVID-19) Trial (ConCorD-19)
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|ClinicalTrials.gov Identifier: NCT04552379|
Recruitment Status : Completed
First Posted : September 17, 2020
Last Update Posted : September 10, 2021
In recent months severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has emerged as a novel human pathogen and, susceptibility amongst humans is presumed to be universal. Prevention measures of COVID-19 have included distancing, quarantines, use of facemasks in public places, and hand hygiene measures. Mandatory quarantines have also been applied on index cases and their contacts, as well as an active search for asymptomatic patients.
Current strategies to reduce the spread of SARS-CoV-2 do not include measures that could prevent transmission prior to the onset of symptoms. Subjects infected with SARS-CoV-2 have been known to shed virus and be contagious for up to 5 days prior to developing symptoms ('pre-symptomatic transmission'). In fact, nearly 60% of all infected subjects can shed virus pre-symptomatically. Pre- or even asymptomatic shedding occurs across all age groups, contributing to the rapidly expanding pandemic.
Post-exposure prophylaxis (PEP) using type 1 interferon (IFN) can potentially eliminate the spread of SARS-CoV-2. IFN could reduce the period of viral shedding by ~1 week. Since pre-symptomatic shedding of virus can start up to 5 days prior to symptom onset, our approach of a PEP intervention to all contacts recently exposed to a case could possibly entirely interrupt the spread of the virus, and with that, the pandemic. The current study focuses on prevention of the disease in addition to its treatment. Thus, the key distinction between these other trials and this study is that this study focuses on containing coronavirus (i.e. cause) in the community, rather than simply its treatment (i.e. consequence) in the individual.
Viral spread could be eliminated through interventions effective at abolishing viral transmission. However, such post-exposure prophylaxis interventions, that is initiation of antiviral therapy in pre-infectious contacts to reduce or even eliminate such spread, must be safe since they are given to asymptomatic and possibly uninfected subjects. In none of the previous clinical trials of IFN therapy for SARS-CoV-2 have serious adverse events been recorded. Furthermore, the IFN chosen for this study (pegylated IFN 1b) has been extensively studied in clinical trials, and has been in clinical use for years for multiple sclerosis. Pegylated IFN formulations allow for weekly injections while maintaining serum levels and limiting dose-dependent side effects. Together these data support a sound safety profile for the planned intervention.
The aim of this study is to ascertain whether IFN administered to index cases and household contacts of an index case, starting immediately following confirmed exposure (index case confirmed positive for SARS-CoV-2), will reduce duration of SARS-CoV-2 detectable by PCR in the index cases, and incidence of SARS-CoV-2 detectable by PCR in household contacts.
|Condition or disease||Intervention/treatment||Phase|
|SARS-CoV Infection Interferon Covid19||Biological: Peginterferon beta-1a||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1173 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
A prospective, cluster randomised trial of interferon versus standard of care. Index cases will be identified from databases of positive COVID-19 PCR patients from the virology lab,('Fever') clinics, outpatient clinics and hospital emergency room visits for possible COVID-19. Household contacts will be identified via the index cases and will be approached with the consent of the index case.
Randomisation: Households will be randomised to receive IFN or standard of care (as recommended by the Public Health Department).
Trial population: Index cases positively infected with SARS-CoV-2 and their exposed household contacts. Index cases will be recruited from databases of individuals with confirmed COVID-19 identified from COVID-19 ('Fever') clinics and emergency room visits in Santiago, Chile.
Eligibility criteria: Households will be randomised only if cases and at least one treatment-eligible household contact meets all the inclusion criteria and none of the exclusion criteria.
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Cluster Randomised Trial of Interferon Versus Standard of Care in the Reduction of Transmission of SARS-Cov-2. The Containing Coronavirus Disease 19 Trial (ConCorD-19)|
|Actual Study Start Date :||December 1, 2020|
|Actual Primary Completion Date :||May 31, 2021|
|Actual Study Completion Date :||June 30, 2021|
Active Comparator: Interferon
Peginterferon beta-1alfa will be made available from Biogen Inc. Switzerland. 125 micrograms of pegylated IFNß1alfa (PLEGRIDY, Biogen) administered on Study Days 1, 6 and 11 (i.e. for a total of 3 doses) via subcutaneous injection.
Biological: Peginterferon beta-1a
Administration of trial drug: PLEGRIDY is given by an injection under the skin (subcutaneous injection). It will be administered to participants in accordance with product insert instructions by appropriately trained trial staff for whom administration of subcutaneous injections is within their normal scope of practice (e.g. RN or MD). They will wait for 20 mins after the last individual receives the interferon before leaving a residence. Administering staff will be supplied with appropriate PPE, trained in the use of this equipment and protocols for infection control, and will always attend in pairs.
PLEGRIDY will be administered in the home of the participants. Due to the heat-labile nature of the trial product (storage required at ~4oC) a verified English Spanish version of the product label will be printed by a GMP certified company and applied to the product and patient band just at the time of use.
Other Name: Plegridy
No Intervention: Standard of Care
Standard of Care; following national guidelines regarding self-isolation and infection prevention
- The proportion of index cases shedding SARS-CoV-2, at Day 11, in the active arm compared to the standard of care arm. [ Time Frame: Day 11 ]
- The proportion of household contacts shedding SARS-CoV-2, at Day 11, in the active arm compared to the standard of care arm. [ Time Frame: Day 11 ]
- Duration (in days) of SARS-CoV-2 by PCR of samples taken on study days 1, 6, 11, 16, 21, and 29. [ Time Frame: Days 1,6,11, 21 and 29 ]
- Number of household contacts of participants in the IFN arm with positive upper airway PCR compared to that in the standard of care arm at day 1 & 11, and seroconversion (Ig) over the study period, up to day 29. [ Time Frame: Days 1,11 and 29 ]
- The proportion of infected cases in the active arm that are hospitalised or die due to COVID-19, as compared to the proportion in the standard of care arm. [ Time Frame: Days 1 to 29 ]
- Incidence and severity of reported adverse events in the interferon arm compared to the standard of care arm. [ Time Frame: Days 1 to 29 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04552379
|Pontificia Universidad Católica de Chile|
|Principal Investigator:||Jose A Castro-Rodriguez, MD,PhD||Pontificia Universidad Catolica de Chile, Santiago, Chile|
|Principal Investigator:||Stephen Stick, MD,PhD||Telethon Kids Institute, University of Western Australia, Perth, Australia|
|Study Director:||Arturo Borzutzky, MD||Pontificia Universidad Catolica de Chile, Santiago, Chile|
|Study Chair:||Carolina Iturriaga, NP||Pontificia Universidad Catolica de Chile, Santiago, Chile|
|Study Chair:||Tobias Kollmann, MD,PhD||Telethon Kids Institute, University of Western Australia, Perth, Australia|
|Study Chair:||Eleanor N Fish, PhD||Department of Immunology, University of Toronto, Canada|
|Study Chair:||Cecilia Perret, MD||Pontificia Universidad Catolica de Chile, Santiago, Chile|
|Study Chair:||Diego Garcia-Huidobro, MD,PhD||Pontificia Universidad Catolica de Chile, Santiago, Chile|