Paxlovid for Long COVID

(RECOVER-VITAL Trial)

Recruiting at 73 trial locations

Overseen By Barrie Harper, BSMT (ASCP) PMP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kanecia Obie Zimmerman

Disqualifiers: Acute SARS-CoV-2, Severe anemia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-4 weeks

964 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing various antiviral and other treatments to help people with long-term COVID-19 symptoms. The goal is to see if these treatments can get rid of any remaining virus, stop it from becoming active again, or calm down the immune system. Participants will receive different treatments to find out which works best.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that participants must be able to discontinue symptomatic medications for certain time periods. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Paxlovid for Long COVID?

Some case series suggest that a 5-day course of Paxlovid may help people with Long COVID, although longer courses have not been studied. Paxlovid has been shown to reduce the risk of severe illness in people with COVID-19, which might indicate potential benefits for Long COVID as well. ^{1 2 3 4 5}

Is Paxlovid safe for humans?

Paxlovid (nirmatrelvir/ritonavir) has been shown to be generally safe in humans, with studies indicating it reduces hospitalization and death in COVID-19 patients. Some side effects include temporary increases in blood pressure and heart rate, but these were observed only at high doses in animal studies. ^{1 2 5 6 7}

What makes Paxlovid unique for treating Long COVID?

Paxlovid is unique for Long COVID as it is an antiviral drug originally used to treat COVID-19, and it works by inhibiting a key enzyme (protease) that the virus needs to replicate. This mechanism is different from other treatments that may focus on managing symptoms rather than targeting the virus itself. ^{8 9 10 11 12}

Research Team

Kanecia Zimmerman, MD PhD

Principal Investigator

Duke University

Richard Whitley, MD

Principal Investigator

University of Alabama at Birmingham Medical Center

Eligibility Criteria

This trial is for adults who've had COVID-19 and are now experiencing Long COVID symptoms persisting for at least 12 weeks. Participants should be able to give consent, complete surveys, and attend follow-up visits. Those with active SARS-CoV-2 infection within the last 4 weeks, severe anemia, moderate/severe immunocompromise, or known allergies to study drugs cannot join.

Inclusion Criteria

I am 18 years old or older.

I have had a COVID-19 infection before.

Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster

Exclusion Criteria

Known severe anemia, defined as < 8 g/dL

Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines

Currently enrolled in another clinical trial outside this platform protocol or another study intervention appendix in this platform protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Paxlovid or placebo for 15 to 25 days depending on the study arm

3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8-10 weeks

Treatment Details

Interventions

• Paxlovid
• Placebo

Trial Overview The RECOVER-VITAL trial is testing Paxlovid's effectiveness in treating Long COVID symptoms over two different durations: a 25-day course and a shorter 15-day course. A control group receives a placebo. The study aims to see if antivirals can clear lingering virus or reduce inflammation that might cause Long COVID.

Participant Groups

Group I: Experimental: Paxlovid 25 day dosing Experimental Treatment 1 Intervention

Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Group II: Experimental: Paxlovid 15 day dosing Experimental Treatment 1 Intervention

Drug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)

Group III: Placebo Comparator: Control Placebo Group 1 Intervention

Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)

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?

Kanecia Obie Zimmerman

Lead Sponsor

Trials

9

Recruited

3,300+

Findings from Research

A case series of 13 individuals with Long COVID who took extended courses of oral nirmatrelvir/ritonavir (7.5-30 days) showed that some experienced a meaningful reduction in symptoms, although the benefits were not consistent for all participants.

While some individuals reported improvements, one participant experienced significant side effects (intense stomach pain), highlighting the need for further research to determine who may benefit from this treatment and the optimal duration for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations. Cohen, AK., Jaudon, TW., Schurman, EM., et al.[2023]

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]

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, a component of Paxlovid, shows a stronger interaction with the SARS-CoV-2 main protease (Mpro) compared to ritonavir, suggesting it plays a key role in the drug's antiviral efficacy.

The study indicates that Paxlovid may remain effective against new COVID-19 variants, such as Omicron, due to the Mpro mutation P132H not affecting the drug's target site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir). Dawood, AA.[2023]

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]

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]

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]

In two pilot studies involving patients with relapsing-remitting multiple sclerosis, the higher dose of TV-5010 (30 mg/week) significantly reduced the number of MRI-active lesions, showing a 58.8% reduction in gadolinium-enhancing lesions and a 50% reduction in new T2-weighted lesions.

Both doses of TV-5010 were generally well tolerated, but the lower dose (15 mg/week) did not demonstrate significant efficacy, indicating that the 30 mg/week dose may be more effective and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis. De Stefano, N., Filippi, M., Confavreux, C., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir). [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study. [2023]

6. Malaysia pubmed.ncbi.nlm.nih.gov

Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Nonclinical Safety Assessment of Nirmatrelvir Supporting Timely Development of the SARS-COV-2 Antiviral Therapeutic, Paxlovid™. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A review of the ethics of the use of placebo in clinical trials for relapsing-remitting multiple sclerosis therapeutics. [2017]

10. Italy pubmed.ncbi.nlm.nih.gov

Long-term treatment response in rheumatoid arthritis patients starting adalimumab or etanercept with or without concomitant methotrexate. [2017]

11. England pubmed.ncbi.nlm.nih.gov

The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Extending rituximab dosing intervals in patients with MS during the COVID-19 pandemic and beyond? [2020]