Paxlovid for Long COVID

(RECOVER-VITAL Trial)

No longer recruiting at 75 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Paxlovid, an antiviral medication, can improve symptoms in people with Long COVID. Researchers are investigating if a persistent viral infection or an overactive immune response causes lasting COVID-19 symptoms and whether Paxlovid could help by clearing the virus or reducing inflammation. The study includes different treatment groups: some participants will receive Paxlovid for varying durations, while others will receive a placebo (a non-active treatment) for comparison. Suitable candidates have had COVID-19 and continue to experience moderate to severe symptoms lasting at least 12 weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that Paxlovid, a treatment being tested for Long COVID, has generally been safe in past studies. One study found that patients tolerated a 15-day course of Paxlovid well, with no major safety concerns, although it didn't significantly reduce symptoms like fatigue. Paxlovid is already approved for treating COVID-19 in high-risk adults, suggesting its relative safety. Overall, the evidence supports that Paxlovid is generally safe for use in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Paxlovid for Long COVID because it targets the virus with a combination of nirmatrelvir and ritonavir, potentially reducing symptoms more effectively than current options, which often focus on symptom management rather than the underlying viral replication. Nirmatrelvir works by inhibiting a key enzyme the virus needs to multiply, while ritonavir boosts its effectiveness. Unlike other treatments that may take weeks or months to show results, Paxlovid has the potential to show improvements in symptoms within days or weeks, offering new hope for those suffering from Long COVID.

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

Research suggests that Paxlovid, a combination of nirmatrelvir and ritonavir, might help some people with Long COVID symptoms. In this trial, participants will receive either a 25-day or 15-day dosing regimen of Paxlovid, or a placebo. Longer use of Paxlovid has shown potential benefits in easing these ongoing symptoms. However, not all studies have found significant improvement compared to a placebo, which contains no active medicine. While Paxlovid is known to reduce the risk of severe COVID-19, its effectiveness in treating Long COVID remains under investigation. Early results indicate it might be helpful, but more research is needed to confirm its efficacy for everyone. ^{1 2 3 6 7}

Who Is on the Research Team?

Richard Whitley, MD

Principal Investigator

University of Alabama at Birmingham Medical Center

Kanecia Zimmerman, MD PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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 have had a COVID-19 infection before.

Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster

Willing and able to provide informed consent, complete the surveys, clinical assessments, and return for all of the necessary follow-up visits

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

Citations

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The STOP-PASC Randomized Clinical Trial - PubMed - NIH There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between ...

2. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(25)00073-8/fulltext

a double-blind, randomised, placebo-controlled, phase 2, ... Post-COVID-19 condition, also known as long COVID or post-acute sequelae of SARS-CoV-2 infection, affects approximately 7–10% of patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05576662

Paxlovid for Treatment of Long Covid (STOP-PASC) The purpose of this study is to compare whether being treated with nirmatrelvir plus ritonavir for 15 days works better than being treated with placebo plus ...

4. academic.oup.com academic.oup.com/ofid/article/12/8/ofaf449/8221041

Patient-Reported Outcomes of Nirmatrelvir Treatment for High ... Approval was based primarily on data from the pivotal phase 2/3 study, which demonstrated an 86% reduction in risk of COVID-19-related ...

5. nature.com nature.com/articles/s43856-024-00668-8

Impact of extended-course oral nirmatrelvir/ritonavir in ... Our results suggest that extended courses of nirmatrelvir/ritonavir could be beneficial for some people with Long COVID.

6. fda.gov fda.gov/media/166238/download

James Rusnak, MD, PhD Senior Vice ... For the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID 19, ...

7. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2819901

Nirmatrelvir-Ritonavir and Symptoms in Adults With ... A 15-day course of nirmatrelvir-ritonavir in a mostly vaccinated study cohort was generally safe, but did not show significant benefit in improving fatigue, ...