Paxlovid for COVID-19

(CanTreatCOVID Trial)

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Unity Health Toronto

Must not be taking: Paxlovid

Disqualifiers: Hospitalized, Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Paxlovid (an antiviral medication) and antioxidant therapy in treating COVID-19 symptoms in non-hospitalized individuals. The main focus is on reducing hospital stays and deaths while helping people recover faster. Participants may receive supportive care, Paxlovid, or antioxidant therapy, which includes vitamins and minerals like selenium and zinc. Ideal candidates have tested positive for COVID-19, experienced symptoms for less than five days, and have a chronic condition such as asthma or diabetes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking a drug that is contraindicated or not recommended with Paxlovid, you may need to stop it. Please consult with the trial investigator for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Paxlovid, a combination of nirmatrelvir and ritonavir, is generally well-tolerated for treating COVID-19. Studies have found that it lowers the risk of serious outcomes like hospitalization and death, indicating its relative safety for use.

Some reports suggest that azvudine, another COVID-19 treatment, might have fewer side effects than Paxlovid. However, Paxlovid remains effective and safe. Countries like China recommend it for COVID-19 treatment, supporting its safety. Overall, evidence suggests that Paxlovid does not usually cause serious problems for most people who take it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Paxlovid for COVID-19 because it combines nirmatrelvir and ritonavir, targeting the virus's ability to replicate, which is different from other treatments that mainly focus on symptom relief or inflammation reduction. This dual-action approach could potentially stop the virus more effectively and quickly. Additionally, Paxlovid is taken orally over just five days, offering a convenient and swift treatment option compared to some other therapies that require longer administration periods or hospital settings.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Studies have shown that Paxlovid, a combination of nirmatrelvir and ritonavir, effectively prevents severe COVID-19 outcomes, such as hospitalization and death. Research indicates it works well for vaccinated individuals and older adults. Real-world evidence supports its ability to reduce the risk of severe symptoms in non-hospitalized individuals. Paxlovid has demonstrated strong activity against current COVID-19 variants, maintaining effectiveness even if the virus changes. In this trial, some participants will receive Paxlovid, while others will receive antioxidant therapy or usual care. Overall, Paxlovid has a proven track record of preventing serious illness from COVID-19. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for Canadians with COVID-19 who aren't hospitalized. It's for those over 50, or 18-49 with conditions like heart disease, diabetes, or weakened immune systems. They must start treatment within 5 days of symptoms and not be in another conflicting COVID-19 drug study.

Inclusion Criteria

I am over 50 or have a chronic condition or a weakened immune system.

I can start the study treatment within 5 days of showing COVID-19 symptoms.

You have tested positive for SARS-CoV-2, and can provide a picture of the positive test result.

Exclusion Criteria

I or my caregiver cannot give informed consent.

I have been in the hospital or emergency department for over 24 hours.

Previously randomized to CanTreatCOVID

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive usual care or a study therapeutic determined by the Canadian COVID-19 Out-Patient Therapeutics Committee

4 weeks

Weekly visits (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of symptom severity and quality of life

36 weeks

Visits at 21 days, 28 days, 90 days, and 36 weeks

Long-term follow-up

Cost-utility analysis and long-term outcomes are assessed

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Paxlovid

Trial Overview The trial compares usual care to Paxlovid and other treatments decided by a committee. Patients are randomly chosen to get either the standard support or a new therapy. The main focus is on whether these prevent hospitalization/death within 28 days and how quickly patients recover.

How Is the Trial Designed?

Group I: Paxlovid Experimental Treatment 1 Intervention

Nirmatrelvir/ritonavir (Paxlovid™) BD x 5 days (this arm has been closed of Sept 30th 2024)

Group II: Antioxidant Therapy - Intervention (arm 3) Experimental Treatment 1 Intervention

Antioxidant therapy (comprising of selenium, zinc, lycopene, and vitamin C)

Group III: Control group Active Control 1 Intervention

Usual care (i.e., supportive care and symptom relief)

Paxlovid is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Paxlovid for:

• COVID-19

Approved in European Union as Paxlovid for:

• COVID-19

Approved in Canada as Paxlovid for:

• COVID-19

Approved in Japan as Paxlovid for:

• COVID-19

Approved in Switzerland as Paxlovid for:

• COVID-19

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Health Canada

Collaborator

Trials

36

Recruited

38,700+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Nirmatrelvir, the active ingredient in Paxlovid, showed a favorable safety profile in nonclinical studies, with no significant adverse effects observed in repeat dose toxicity studies conducted in rats and monkeys for up to one month.

The drug effectively targets the SARS-CoV-2 3CL protease, essential for viral replication, and demonstrated efficacy in high-risk COVID-19 patients, supporting its use in preventing severe outcomes like hospitalization and death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Nonclinical Safety Assessment of Nirmatrelvir Supporting Timely Development of the SARS-COV-2 Antiviral Therapeutic, Paxlovid™. Sathish, JG., Bhatt, S., DaSilva, JK., et al.[2022]

Nirmatrelvir/ritonavir (Paxlovid®) has low-certainty evidence suggesting it significantly reduces the risk of all-cause mortality and hospital admissions in unvaccinated, high-risk COVID-19 patients with mild symptoms, based on a study of 2246 participants.

The treatment appears to be safe, with moderate-certainty evidence indicating it may reduce serious adverse events compared to placebo, although it may increase some treatment-related side effects like dysgeusia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19. Reis, S., Metzendorf, MI., Kuehn, R., et al.[2023]

Paxlovid, which combines nirmatrelvir and ritonavir, is an effective oral antiviral treatment for COVID-19, with nirmatrelvir specifically targeting the SARS-CoV-2 main protease to inhibit viral replication.

Ritonavir enhances the effectiveness of nirmatrelvir by slowing its metabolism, but it also poses a risk for drug interactions due to its role as a CYP3A4 inhibitor, necessitating careful management of other medications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences. Azanza, JR., Mensa, J., González Del Castillo, J., et al.[2022]

In a study of 264 hospitalized adults with severe comorbidities, Paxlovid (nirmatrelvir plus ritonavir) did not significantly reduce all-cause mortality or the duration of SARS-CoV-2 RNA clearance compared to standard treatment alone.

The incidence of adverse events was similar between the Paxlovid group and the standard treatment group, indicating that Paxlovid does not increase safety risks in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study. Liu, J., Pan, X., Zhang, S., et al.[2023]

Nirmatrelvir-ritonavir (Paxlovid®) is an oral treatment for Covid-19 that has been available since February 4, 2022.

It is specifically designed for individuals at very high risk of developing severe forms of the disease, highlighting its targeted use for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. Buxeraud, J., Faure, S., Fougere, É.[2022]

Nirmatrelvir/ritonavir (Paxlovid®) is an effective oral antiviral treatment for COVID-19, showing good tolerability and the potential to prevent severe complications when administered early in mild-to-moderate cases.

While it enhances the efficacy of nirmatrelvir, ritonavir can cause drug-drug interactions that may limit its use in patients on certain chronic medications, and there is a risk of infection relapse after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical discovery and development of nirmatrelvir/ritonavir combinational therapy for the treatment of COVID-19 and the lessons learned from SARS-COV-2 variants. Pagliano, P., Spera, A., Sellitto, C., et al.[2023]

Nirmatrelvir/ritonavir (Paxlovid) shows low-certainty evidence of reducing all-cause mortality and hospital admissions in high-risk, unvaccinated outpatients with mild COVID-19, particularly during the Delta variant wave, based on a review of 2 RCTs involving 2510 participants.

In inpatients with moderate to severe COVID-19, the evidence regarding the efficacy of nirmatrelvir/ritonavir is very low, with no significant findings on mortality or viral clearance, highlighting the need for further research in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19. Reis, S., Metzendorf, MI., Kuehn, R., et al.[2023]

In a study of 552 COVID-19 patients, treatment with Paxlovid® did not significantly reduce hospitalisation rates or all-cause mortality compared to a matched control group, indicating limited effectiveness in this local setting.

While adverse effects from Paxlovid® were common, they were generally not severe, suggesting that while the drug may not lower hospitalisation or death rates, it is relatively safe for use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study. Chew, LS., Lim, XJ., Chang, CT., et al.[2023]

Citations

1. academic.oup.com academic.oup.com/ofid/article/12/9/ofaf553/8246175

Real-World Effectiveness of Nirmatrelvir–Ritonavir Against ... Five outcomes were assessed, including COVID-19-related hospitalization, ICU admission, invasive ventilatory support, death, and the composite ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39823513/

Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization ... We observed that Paxlovid is effective at preventing hospitalization and death, including among vaccinated patients, and particularly among older patients.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223001555

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid ... Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome.

4. vaccineadvisor.com vaccineadvisor.com/news/nirmatrelvir-ritonavir-reduces-risk-for-severe-covid19-outcomes/

Nirmatrelvir-Ritonavir Reduces Risk for Severe COVID-19 ... Real-world data supports the use of nirmatrelvir-ritonavir in reducing the risk for severe COVID-19 outcomes among nonhospitalized patients.

5. acpjournals.org acpjournals.org/doi/10.7326/M22-3565

Effectiveness of COVID-19 Treatment With Nirmatrelvir ... Nirmatrelvir–ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37485774/

Efficacy and safety of paxlovid (nirmatrelvir/ritonavir) in the ... Paxlovid effectively reduced the risks of death, hospitalisation, death or hospitalisation, ED visit, ICU admission, and extra oxygen requirement.

7. nature.com nature.com/articles/s41392-025-02126-w

Real‐world effectiveness and safety of oral azvudine ... These findings suggest that azvudine therapy is not inferior to Paxlovid in hospitalized COVID-19 patients and has fewer adverse effects.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2211383524004891

A retrospective cohort study of the efficacy and safety ... Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11309578/

NIRMATRELVIR/RITONAVIR (PAXLOVID) USE AMONG ... Paxlovid is effective in reducing COVID-19 hospitalization and mortality. This study characterized Paxlovid use and evaluated racial/ethnic disparities over ...