Antiviral Strategies in the Prevention of Long-term Cardiovascular Outcomes Following COVID-19: The paxloviD/Remdesivir Effectiveness For the prEvention of loNg coviD Clinical Trial (DEFEND)

January 23, 2025 updated by: Mount Sinai Hospital, Canada

Antiviral Strategies in the Prevention of Long-term Cardiovascular Outcomes Following COVID-19: The paxloviD/Remdesivir Effectiveness For the prEvention of loNg coviD (DEFEND) Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The overall goal of the DEFEND clinical trial is to study the effectiveness of Paxlovid or Veklury in preventing cardiovascular post-acute among adults who test positive for SARS-CoV-2 at admission to hospital. The pilot trial will inform the design and conduct of a future full-scale multicentre trial by estimating the feasible recruitment rate. Our secondary aim is to validate the accuracy of hospital-based outcome measures in administrative data, and to determine the event rate of a composite of any of 4 newly developed or worsening stroke, heart failure, venous thromboembolism, diabetes or death within 1 year. The DEFEND trial will be a pragmatic, multicentre, registry-based, double-blind, two-arm, randomized placebo-controlled internal pilot trial. If no major protocol changes are required, the data obtained from the pilot will be included in the future large trial; if major protocol changes are required, the results from the pilot trial will still be published and will be useful to inform future research in this area. The approach is pragmatic to include as many participants as possible that could benefit from treatment with Paxlovid or Veklury using broad eligibility criteria for enrolment and reflecting the real world practice of treating physicians. The DEFEND trial will enrol participants aged ≥18 who have a positive polymerase chain reaction test for SARS-CoV-2 at admission to 4 hospitals in Ontario. If they meet the inclusion/exclusion criteria they will be randomized to either the experimental or control arm of the trial. Those in the experimental arm will receive either Paxlovid orally twice daily for 5 days or Veklury intravenously once daily for 5 days (as well as standard of care). Those in the control arm will receive the placebo at the same schedule and frequency for 5 days (as well as standard of care). Randomization will be at a 1:1 allocation, stratified by hospital. The DEFEND trial seeks to enrol 118 participants at 4 committed pilot trial sites that are representative of acute care hospitals across Ontario over a 12 month period. This will be followed by a 12 month follow-up period. 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.

Study Type

Interventional

Enrollment (Estimated)

118

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Not yet recruiting
        • Kingston Health Sciences Centre
        • Contact:
      • St. Catharines, Ontario, Canada, L2S 0A9
      • Toronto, Ontario, Canada, M5G 1X5
        • Recruiting
        • Mount Sinai Hospital, Sinai Health System
        • Contact:
        • Principal Investigator:
          • Dr. Kieran Quinn
        • Sub-Investigator:
          • Dr. Mike Fralick
      • Toronto, Ontario, Canada, M6R 1B5
        • Not yet recruiting
        • St. Joseph's Health Centre, Unity Health Toronto
        • Contact:
        • Principal Investigator:
          • Dr. Travis Carpenter

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥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)

Exclusion Criteria:

  • 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;
  • Limited life expectancy estimated to be ≤3 months;
  • Pregnant and breastfeeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paxlovid
Paxlovid vs. placebo
Drug: Nirmatrelvir/ritonavir
Paxlovid PO BID for 5 days + standard of care
Other Names:
  • Paxlovid
Experimental: Veklury
Veklury vs. placebo
Drug: Remdesivir
Veklury IV daily for 5 days + standard of care
Other Names:
  • Veklury

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment rate
Time Frame: From participant screening to enrolment
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.
From participant screening to enrolment
Post-acute sequelae of COVID-19 (PASC)
Time Frame: From enrolment to end of follow up at 1 year
Event rate of PASC at 1 year (specifically newly developed or worsening: stroke, heart failure, venous thromboembolism, diabetes or death)
From enrolment to end of follow up at 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Administrative data validation
Time Frame: From enrolment to end of follow up at 1 year

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.
From enrolment to end of follow up at 1 year
Reinfection, ICU admission, and drug safety
Time Frame: From enrolment to 90 days after initial PCR positive test for COVID-19

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
From enrolment to 90 days after initial PCR positive test for COVID-19

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mount Sinai Hospital, Canada

Collaborators

Unity Health Toronto
Niagara Health System
Kingston Health Sciences Centre (Kingston)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2025

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

December 23, 2024

First Submitted That Met QC Criteria

January 23, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 23, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UTN: U1111-1311-3673
  • 202309PPE (Other Grant/Funding Number: CIHR)
  • 185352 (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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