SARS CoV-2 Post-Acute SequelaePhase 4DEFENDNCT06792214
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
A Phase 4 study testing Nirmatrelvir/ritonavir and Remdesivir in people with SARS CoV-2 Post-Acute Sequelae, run by Mount Sinai Hospital, Canada at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SARS CoV-2 Post-Acute Sequelae
- What is being tested?
- Nirmatrelvir/ritonavir and Remdesivir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 4 sitesCanada
- Study dates
- 3 Jan 2025to Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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)
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada4 sites, 4 recruiting
- Not yet recruiting
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Dr. Siddhartha Srivastava, 613-533-2780, srivastava.s@queensu.ca
- Not yet recruiting
Niagara Health System
St. Catharines, Ontario, L2S 0A9
Dr. Jennifer Tsang, 905-684-7271, jennifer.tsang@niagarahealth.on.ca
- Recruiting
Mount Sinai Hospital, Sinai Health System
Toronto, Ontario, M5G 1X5
Dr. Kieran Quinn, 416-843-8403, kieran.quinn@mail.utoronto.ca
Dr. Kieran Quinn
- Not yet recruiting
St. Joseph's Health Centre, Unity Health Toronto
Toronto, Ontario, M6R 1B5
Dr. Travis Carpenter, 416-530-6692, travis.carpenter@unityhealth.to
Dr. Travis Carpenter
About this study
Official title: 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.
Read the 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.
- Conditions
- SARS CoV-2 Post-Acute Sequelae
- Being tested
- Nirmatrelvir/ritonavir, Remdesivir
- Keywords
- SARS CoV-2, long covid
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nirmatrelvir/ritonavirDrug
Also called Paxlovid
Paxlovid PO BID for 5 days + standard of care
RemdesivirDrug
Also called Veklury
Veklury IV daily for 5 days + standard of care
| Study group | Role | What they receive |
|---|---|---|
| Paxlovid | Experimental | Paxlovid vs. placebo Receives: Drug: Nirmatrelvir/ritonavir |
| Veklury | Experimental | Veklury vs. placebo Receives: Drug: Remdesivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: From enrolment to end of follow up at 1 year
Secondary outcomes (2)
Administrative data validation
Validate the accuracy of using administrative data to collect participant hospital-based outcome measures including:
- Adherence to treatment, measured by whether the participant received the study drug or not as documented in the medication administration record.
- Use of co-interventions (dexamethasone, tocilizumab/sarilumab, baricitinib) owing to progression of disease severity as measured by spO2 <92%
- 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.
Measured: From enrolment to end of follow up at 1 year
Reinfection, ICU admission, and drug safety
Any of the following treatment related adverse events as assessed with the CTCAE v6.0:
- Number and percentage of participants hospitalized with SARS-CoV-2 reinfection within 90 days following initial PCR positive test for COVID-19;
- Number and percentage of participants admitted to ICU during initial hospitalization;
- 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
Measured: From enrolment to 90 days after initial PCR positive test for COVID-19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2025
- Study start3 Jan 2025
- Primary completionJan 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SARS CoV-2 Post-Acute SequelaeStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Unity Health Toronto, Kingston Health Sciences Centre, Niagara Health System
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06792214
- Sponsor's protocol ID
- UTN: U1111-1311-3673
- Other IDs
- 202309PPE, 185352
- Acronym
- DEFEND
- Status last verified
- Dec 2024
- First submitted
- 23 Dec 2024
- Last updated
- 24 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06792214
- Acronym / sponsor ID
- DEFEND / UTN: U1111-1311-3673
- Conditions
- SARS CoV-2 Post-Acute Sequelae
- Keywords
- SARS CoV-2, long covid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Unity Health Toronto, Kingston Health Sciences Centre, Niagara Health System
- Study start
- 3 Jan 2025 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 24 Jan 2025 (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.
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.
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 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 |
|---|---|---|
| Paxlovid | Experimental | Drug: Nirmatrelvir/ritonavirPaxlovid vs. placebo |
| Veklury | Experimental | Drug: RemdesivirVeklury vs. placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ≥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)
Key exclusion criteria (6 listed)
- 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;
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 |
|---|---|---|
| Nirmatrelvir/ritonavirAlso: PaxlovidPaxlovid PO BID for 5 days + standard of care | Drug | Paxlovid |
| RemdesivirAlso: VekluryVeklury IV daily for 5 days + standard of care | Drug | Veklury |
Primary outcome
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.
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)
2 secondary outcomes
Administrative data validation
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Individual participant dataSharing planned: Undecided
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nirmatrelvir/ritonavir and Remdesivir in people with SARS CoV-2 Post-Acute Sequelae, run by Mount Sinai Hospital, Canada at 4 sites 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 4 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 24 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Kieran Quinn (416-843-8403, kieran.quinn@mail.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment rate (time frame: From participant screening to enrolment). The study lists 2 primary outcomes in all. 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 24 Jan 2025.