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

NCT06792214 | Recruiting Phase 4 DMC

• 3 other identifiers: UTN: U1111-1311-3673202309PPE185352
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

SARS CoV-2 Post-Acute Sequelae

Keywords

SARS CoV-2; long covid

Outcome Measures

Primary Outcomes (2)

• 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.

  From participant screening to enrolment

• 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)

  From enrolment to end of follow up at 1 year

Secondary Outcomes (2)

• Administrative data validation

  From enrolment to end of follow up at 1 year

• Reinfection, ICU admission, and drug safety

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

Study Arms (2)

Paxlovid

EXPERIMENTAL

Paxlovid vs. placebo

Drug: Nirmatrelvir/ritonavir

Veklury

EXPERIMENTAL

Veklury vs. placebo

Drug: Remdesivir

Interventions

Nirmatrelvir/ritonavir DRUG

Paxlovid PO BID for 5 days + standard of care

Also known as: Paxlovid

Paxlovid

Remdesivir DRUG

Veklury IV daily for 5 days + standard of care

Also known as: Veklury

Veklury

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Unity Health Toronto: collaborator
• Kingston Health Sciences Centre: collaborator
• Niagara Health System: collaborator

Study Sites (4)

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

NOT YET RECRUITING

Niagara Health System

St. Catharines, Ontario, L2S 0A9, Canada

NOT YET RECRUITING

Mount Sinai Hospital, Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

St. Joseph's Health Centre, Unity Health Toronto

Toronto, Ontario, M6R 1B5, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

nirmatrelvir and ritonavir drug combination; remdesivir

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr. Kieran Quinn

CONTACT

416-843-8403; kieran.quinn@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: January 24, 2025
• Study Start: January 3, 2025
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 24, 2025

Record last verified: 2024-12

Locations

CA (4)