The DEFEND trial will be the world's first clinical trial to study the effectiveness of Paxlovid or Veklury in the prevention of cardiovascular post-acute sequelae of SARS-CoV-2 among hospitalized adults. Additionally, this pilot study will inform the design and conduct of a future full-scale multi-centre trial by testing the feasibility and accuracy of this study design.
≥18 years old
Positive PCR test for SARS-CoV-2 within 5 days of admission to hospital
Normoxic (not receiving supplemental oxygen)
Able to provide informed written consent (or, if patient is unable, have substitute decision maker available)
Absolute contraindications to Paxlovid or Veklury (any of the following): Severe allergy to Paxlovid or Veklury (e.g. anaphylaxis), co-administration with drugs highly dependent on CYP3A for clearance, co-administration with potent CYP3A inducers
Exposure to Paxlovid or Veklury within previous 14 days;
Receiving supplemental oxygen;
Known positive SARS-CoV-2 PCR or rapid antigen test 5-90 days prior to admission;
Parallel
Nirmatrelvir/ritonavir
DrugPaxlovid PO BID for 5 days + standard of care
Remdesivir
DrugVeklury IV daily for 5 days + standard of care
Recruitment rate
Recruitment rate, defined as the proportion of eligible people who consent and are randomized into the pilot trial, which will inform the feasibility of a full scale trial.
Post-acute sequelae of COVID-19 (PASC)
Event rate of PASC at 1 year (specifically newly developed or worsening: stroke, heart failure, venous thromboembolism, diabetes or death)
Administrative data validation
Validate the accuracy of using administrative data to collect participant hospital-based outcome measures including: 1. Adherence to treatment, measured by whether the participant received the study drug or not as documented in the medication administration record. 2. Use of co-interventions (dexamethasone, tocilizumab/sarilumab, baricitinib) owing to progression of disease severity as measured by spO2 \<92% 3. Time to treatment initiation, as measured by the time between randomization and first treatment dose. The validation of administrative data will be assessed by comparing concordance between manually collected data by research coordinators entered into REDCap and the GEMINI administrative database for the measures described above.
Reinfection, ICU admission, and drug safety
Any of the following treatment related adverse events as assessed with the CTCAE v6.0: 1. Number and percentage of participants hospitalized with SARS-CoV-2 reinfection within 90 days following initial PCR positive test for COVID-19; 2. Number and percentage of participants admitted to ICU during initial hospitalization; 3. Number and percentage of participants experiencing any one of the following adverse study drug effects including dysgeusia, vomiting, or diarrhea as identified by their most responsible physician
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Mount Sinai Hospital, Canada
Lead sponsor
Unity Health Toronto
Collaborator
Kingston Health Sciences Centre
Collaborator
Niagara Health System
Collaborator
