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

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study is being done to answer the question: Does the use of statin lipid-lowering medication change the effect of influenza vaccine? The research team will use the knowledge gained from answering this question to understand how this medication affects long-lasting immune responses to vaccines. The researchers will study the immune response to the influenza vaccine in the blood (where antibodies are). The team will also look at how statin therapy affects the bacteria that live in the gut by collecting stool samples. To be in this research, participants must be adults willing to receive vaccines.

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.

Is the quadrivalent influenza vaccine generally safe for humans?

The quadrivalent influenza vaccine (QIV) is generally safe for humans, with most reported side effects being mild, such as injection site reactions, fever, headache, and nausea. Serious side effects are rare, and no new safety concerns have been identified in recent studies. ^{1 2 3 4 5}

How is the quadrivalent seasonal influenza vaccine different from other flu vaccines?

The quadrivalent seasonal influenza vaccine (QIV) is unique because it includes two A strains and two B lineages, which helps prevent a mismatch with circulating flu strains, unlike the trivalent vaccine that only covers one B lineage. ^{3 4 6 7 8}

What data supports the effectiveness of the treatment Atorvastatin for Vaccine Response?

The research highlights the effectiveness of quadrivalent influenza vaccines (QIV) in preventing influenza, which is part of the treatment being studied. These vaccines are designed to protect against four different flu viruses, and studies show they are increasingly used in healthcare to prevent influenza. ^{3 7 9 10 11}

Who Is on the Research Team?

Nadine Rouphael, MD

Principal Investigator

Emory University

Varun Phadke, MD

Principal Investigator

Emory University

Vin Tangpricha, MD, PhD

Principal Investigator

Emory University

Daniel S. Graciaa, MD, MPH, MSc

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 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]

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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Immunogenicity and Safety of the Quadrivalent Adjuvant Subunit Influenza Vaccine in Seropositive and Seronegative Healthy People and Patients with Common Variable Immunodeficiency. [2023]

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

Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial. [2022]

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

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

4. Netherlands 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. [2018]

5. Netherlands 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. [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years. [2018]

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

Three seasons of enhanced safety surveillance of a cell culture-based quadrivalent influenza vaccine. [2023]

10. Netherlands 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. [2019]

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

From trivalent to quadrivalent influenza vaccines: Public health and economic burden for different immunization strategies in Spain. [2020]