Atorvastatin for Vaccine Response

Overseen By Daniel S. Graciaa, MD, MPH, MSc

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Statins, Lipid-lowering drugs

Disqualifiers: Impaired immunity, HIV, Hepatitis, others

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

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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a cholesterol-lowering medication called a statin might alter the effectiveness of the flu vaccine. Researchers aim to determine if taking a statin affects the body's immune response to the flu shot and its impact on gut bacteria. Participants will either receive a flu vaccine alone or take a statin before getting the flu vaccine. Adults willing to receive a flu shot and not currently on statins or facing certain health issues may be suitable for this study. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently using statins or any other lipid-lowering drugs. Also, if your medication interacts with statin therapy, you may not be eligible for the statin therapy group.

What is the safety track record for these treatments?

Research has shown that atorvastatin, a common cholesterol-lowering medication, is generally safe. However, some studies suggest that people taking statins might respond slightly less effectively to the flu vaccine compared to those not on statins. This does not imply the vaccine is unsafe; it may simply be less effective.

Regarding side effects, one study found a rare risk of muscle problems, such as rhabdomyolysis (a serious condition where muscles break down), when combining statins with the flu vaccine. However, this occurrence is uncommon. The FDA has approved statins for a long time, and doctors are experienced in managing any side effects. Overall, atorvastatin is considered safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard approach of simply administering the seasonal quadrivalent influenza vaccine (QIV), this trial explores the combination of statin therapy with the vaccine. Researchers are excited about this new approach because statins, typically used to manage cholesterol, may enhance the immune response to vaccines. The unique angle here is the potential for statins to boost vaccine effectiveness, offering a novel way to improve protection against the flu. This could be particularly beneficial for individuals with weaker immune systems, potentially providing them with better defense during flu season.

What evidence suggests that this trial's treatments could be effective for vaccine response?

This trial will compare the effects of atorvastatin combined with a seasonal quadrivalent influenza vaccine (QIV) to the QIV alone. Research has shown that atorvastatin, a common cholesterol-lowering drug, can increase the production of certain antibodies after vaccination, potentially enhancing the body's response. However, some studies found that statins might reduce the flu vaccine's effectiveness, although these studies did not focus on confirmed flu cases. Thus, evidence on atorvastatin's impact on the flu vaccine remains mixed. The seasonal flu vaccine protects against four different types of flu, offering broad protection during flu season. ^{1 4 6 7 8}

Who Is on the Research Team?

Daniel S. Graciaa, MD, MPH, MSc

Principal Investigator

Emory University

Nadine Rouphael, MD

Principal Investigator

Emory University

Varun Phadke, MD

Principal Investigator

Emory University

Vin Tangpricha, MD, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

Adults aged 18-50 who can consent and agree to use birth control if of childbearing potential. Excluded are those with impaired immunity, serious chronic conditions, BMI over 30, current or past statin use, pregnancy/breastfeeding intentions within study period, recent vaccine receipt or infection.

Inclusion Criteria

I understand the study and agree to participate.

Women of childbearing potential must agree to use effective birth control for the first 3 months of the study. A negative urine pregnancy test must be documented prior to vaccination

Exclusion Criteria

You are currently taking or have taken Statin

I do not have severe health issues or recent major medical changes.

You are currently taking or have taken Statin

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Statin Therapy Initiation

Participants randomized to the Statin + QIV arm will start statin therapy one month prior to vaccination

4 weeks

1 visit (in-person)

Vaccination

Participants receive the seasonal quadrivalent influenza vaccine (QIV)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after vaccination, including collection of blood and stool samples

29 days

Multiple visits (in-person)

Extended Follow-up

Participants are monitored for serious adverse events up to 181 days after vaccine administration

152 days

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Quadrivalent seasonal influenza vaccine

Trial Overview

The trial is investigating how Atorvastatin (a cholesterol-lowering drug) affects the immune response to a flu vaccine. It involves blood tests for antibodies and stool samples to study gut bacteria changes after vaccination.

How Is the Trial Designed?

Group I: statin therapy and a seasonal quadrivalent influenza vaccine (QIV) Active Control 2 Interventions

Participants randomized to the Statin + QIV arm will be asked to come back for an extra visit one month prior to the date of vaccination to start statin therapy.

Group II: seasonal quadrivalent influenza vaccine (QIV) Active Control 1 Intervention

Participants will receive the seasonal QIV

Quadrivalent seasonal influenza vaccine is already approved in United States, Canada, European Union, Japan for the following indications:

Approved in United States as Fluarix Quadrivalent for:

• Prevention of influenza A and B in individuals 6 months of age and older

Approved in Canada as Flulaval Quadrivalent for:

• Prevention of influenza A and B in individuals 6 months of age and older

Approved in European Union as Fluzone Quadrivalent for:

• Prevention of influenza A and B in individuals 6 months of age and older

Approved in Japan as Quadrivalent seasonal influenza vaccine for:

• Prevention of influenza A and B in individuals 6 months of age and older

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

The quadrivalent influenza vaccine (QIV) demonstrated similar efficacy to the trivalent influenza vaccine (TIV) for the three common strains, but showed superior immunogenicity for the additional B lineages not included in TIV, with significant increases in seroprotection and seroconversion rates.

Both QIV and TIV had comparable safety profiles, with no serious adverse events reported; however, QIV was associated with a slightly higher incidence of injection-site pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials. Moa, AM., Chughtai, AA., Muscatello, DJ., et al.[2018]

The Fluzone Intradermal (ID) vaccine was found to be as immunogenic as the standard intramuscular (IM) vaccine, showing no significant differences in antibody responses for all three viral strains tested.

While the ID vaccine had higher rates of local reactions like erythema and swelling compared to the IM vaccine, it was well-tolerated overall, with no serious adverse events reported, indicating it can be safely used for annual revaccination in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age. Gorse, GJ., Falsey, AR., Johnson, CM., et al.[2013]

A new active surveillance system called SICOVA was developed in Mexico to monitor adverse events (AEs) following quadrivalent influenza vaccination, involving 2013 participants over three influenza seasons.

The overall adverse event rate was 9.09%, with most AEs being mild and not requiring medical visits, confirming the established safety profile of the Fluzone® Quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system. Betancourt-Cravioto, M., Cervantes-Powell, P., Tapia-Conyer, R., et al.[2022]

The quadrivalent influenza vaccine S-IIV4 demonstrated noninferior immunogenicity compared to the US-licensed C-IIV4 in a study involving 2,247 children aged 6-59 months, indicating it effectively stimulates the immune response against influenza strains.

S-IIV4 was associated with lower rates of fever (5.8%) compared to C-IIV4 (8.4%), suggesting improved safety in terms of febrile reactions, with no reports of febrile convulsions in either vaccine group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study. Statler, VA., Albano, FR., Airey, J., et al.[2019]

Switching from the trivalent influenza vaccine (TIV) to the quadrivalent influenza vaccine (QIV) in Spain could prevent approximately 138,707 cases of influenza B each season, leading to significant reductions in outpatient visits, hospitalizations, and deaths.

The economic analysis suggests that this switch could save over €18 million annually in healthcare costs and productivity losses, making QIV a cost-effective intervention for the Spanish National Health Service, particularly benefiting those aged 65 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From trivalent to quadrivalent influenza vaccines: Public health and economic burden for different immunization strategies in Spain. Crépey, P., Redondo, E., Díez-Domingo, J., et al.[2020]

The high-dose quadrivalent influenza vaccine (QIV-HD) was approved for individuals 65 years and older, and a review of 2,122 adverse event reports showed that 95.1% were non-serious, aligning with findings from prelicensure trials.

No new safety concerns were identified, with the most common serious events being Guillain-Barré syndrome and local reactions, suggesting that QIV-HD is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Woo, EJ., Moro, PL.[2022]

The high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

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