Vaccination Program for Flu

(Influential Trial)

Recruiting at 1 trial location

Overseen By Suchitra Rao

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Disqualifiers: Critical care, Hematology-oncology

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

Compensation: Varies

Number of Visits: Unknown

22000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new, standardized flu vaccination program can increase flu shot rates among children in hospitals across the U.S. The study tests a detailed plan that includes enhanced education and communication about the vaccine, data tools, and input from experts such as doctors and parents. Two groups participate: one uses the new structured program, while the other follows existing influenza vaccination practices. Children at least six months old and staying in a non-critical care section of a participating hospital may qualify for this trial. As an unphased trial, this study offers an opportunity to contribute to improving flu vaccination strategies for children nationwide.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this standardized inpatient influenza vaccination program is safe?

Research shows that flu vaccines are generally safe for most people. Studies have found that these vaccines can significantly reduce hospital visits due to flu-related issues, with protection lasting over 120 days after vaccination. This means the vaccine provides long-lasting protection.

However, some reports mention possible side effects. In rare cases, children and teens had a higher risk of developing narcolepsy, a sleep disorder, after receiving the vaccine. Adults also faced an increased risk, though it was lower than in children. Most people experience only mild side effects, such as soreness at the injection site or a slight fever.

Overall, the vaccines used in the program have undergone thorough study. They are considered safe and effective for preventing the flu and reducing hospital visits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the new influenza vaccination program because it offers a more structured and comprehensive approach compared to existing inpatient practices. Unlike the usual care, which varies greatly between sites, this program uses informatics and data analytics to streamline the vaccination process. It also integrates evidence-based education and communication strategies, supported by a multidisciplinary leadership team, to enhance patient and staff engagement. Additionally, an intensified version of the program introduces a learning collaborative with lead site facilitation, aiming to boost vaccination rates and improve health outcomes during the trial period.

What evidence suggests that this trial's vaccination programs could be effective for increasing flu vaccination rates in hospitalized children?

This trial will compare a standardized inpatient influenza vaccination program with existing inpatient practices. Studies have shown that organized hospital programs can increase flu vaccination rates among children. Research indicates that the flu vaccine can reduce the risk of hospitalization due to the flu by about 58%. Additionally, receiving the flu shot is associated with a 30% decrease in flu-related deaths. These programs typically include tools for data analysis, education, and improved communication to enhance vaccination efforts. The goal is to ensure more children receive vaccinations, leading to fewer flu-related health issues. ^{3 6 7 8 9}

Who Is on the Research Team?

Suchitra Rao

Principal Investigator

University of Colorado, Children's Hospital Colorado

Are You a Good Fit for This Trial?

The INFLUENTIAL Trial is for hospitalized children at least 6 months old in participating US health systems, excluding those admitted to critical care or hematology-oncology services. It aims to see if a new program can improve flu vaccination rates.

Inclusion Criteria

I am at least 6 months old.

Admitted to an inpatient unit at a participating health system

I am admitted to a critical care or cancer treatment unit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implementation

Implementation of a standardized inpatient influenza vaccination program across 12 health systems

12 months

Evaluation

Evaluation of the program's impact using an established dissemination and implementation framework

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after the implementation of the vaccination program

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Existing Influenza Vaccination Practices
• Standardized inpatient influenza vaccination program

Trial Overview This trial tests whether a standardized inpatient influenza vaccination program, developed with input from various healthcare stakeholders and parents, can increase the number of hospitalized children getting flu shots.

How Is the Trial Designed?

Group I: Standardized inpatient influenza vaccination program Active Control 1 Intervention

Intervention A: The basic intervention is the inpatient influenza vaccination program, which will be comprised of the following core components: informatics and data analytic tools, evidenced-based education and communication, a multidisciplinary leadership team, and end-user engagement. Intervention B: The intensified intervention is the multifaceted influenza vaccination strategy (Intervention A) plus a learning collaborative with lead site facilitation during the trial period.

Group II: Existing inpatient influenza vaccination practices Active Control 1 Intervention

Usual care is defined as the inpatient influenza vaccination practices that currently exist at a given site.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Agency for Healthcare Research and Quality (AHRQ)

Collaborator

Trials

415

Recruited

6,777,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

The CDC recommends annual influenza vaccination for everyone aged 6 months and older, updating the vaccine formulations for the 2013-14 season to include quadrivalent options that cover more virus strains.

New vaccines approved include the quadrivalent live attenuated influenza vaccine (LAIV4) and quadrivalent inactivated influenza vaccine (IIV4), which provide broader protection by including an additional B virus strain, ensuring coverage of both influenza B lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014. [2022]

The high-dose trivalent inactivated influenza vaccine (IIV3-HD) is more effective than the standard-dose vaccine (IIV3-SD) in protecting adults aged 65 and older from influenza, as shown in a systematic review of seven studies.

IIV3-HD is also cost-effective or cost-saving compared to IIV3-SD, primarily due to a reduction in hospitalizations for cardiorespiratory events, highlighting its economic benefits in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic evaluation of high-dose inactivated influenza vaccine in adults aged ≥65 years: A systematic literature review. Colrat, F., Thommes, E., Largeron, N., et al.[2021]

In a study involving over 3.8 million older adults with health conditions during the 2017-2019 influenza seasons, the MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) was found to be significantly more effective than the standard quadrivalent inactivated influenza vaccine (IIV4) in preventing influenza-related medical encounters, with a relative vaccine effectiveness increase of 7.1% in 2017-2018 and 20.4% in 2018-2019.

The high-dose trivalent inactivated influenza vaccine (HD-IIV3) showed comparable effectiveness to aIIV3, indicating that both enhanced vaccines provide better protection for older adults who are at higher risk for influenza complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of the Adjuvanted Influenza Vaccine in Older Adults at High Risk of Influenza Complications. Boikos, C., Imran, M., Nguyen, VH., et al.[2021]

The inactivated quadrivalent influenza vaccine (IIV4) was found to be safe and well-tolerated in a phase III trial involving 1,648 adults and 329 children/adolescents, with no serious adverse events reported.

IIV4 induced strong antibody responses to all four influenza strains it targets, meeting all immunogenicity criteria set by the European Medicines Agency, and showed comparable efficacy to the trivalent vaccine (IIV3) in both age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Cadorna-Carlos, JB., Nolan, T., Borja-Tabora, CF., et al.[2015]

A review of safety data for the high-dose influenza vaccine (IIV3-HD) in adults aged 65 and older from 2011 to 2019 found no new or unexpected safety concerns, with serious adverse events reported in only 5.9% of cases.

Inadvertent administration of IIV3-HD to children and pregnant women occurred, but no serious adverse events were reported, highlighting the need for better training and education for healthcare providers on vaccine recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the safety of high-dose, trivalent inactivated influenza vaccine in the vaccine adverse event reporting system (VAERS), 2011 - 2019. Moro, PL., Woo, EJ., Marquez, P., et al.[2021]

The MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) showed consistent effectiveness over standard egg-based quadrivalent vaccines (IIV4e) in preventing influenza-related medical encounters among adults aged 65 and older during the 2017-2020 influenza seasons.

When compared to the high-dose influenza vaccine (HD-IIV3), aIIV3 provided better overall benefits while showing comparable effectiveness in at-risk populations, indicating its potential as a superior option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine over Three Consecutive Influenza Seasons in the United States. Boikos, C., McGovern, I., Ortiz, JR., et al.[2022]

The quadrivalent inactivated influenza vaccine (IIV4) showed a noninferior immune response compared to the trivalent vaccines (IIV3-YAM and IIV3-VIC) for matched strains, and a superior response for unmatched B strains, based on a study involving 3484 adults.

Safety profiles were similar across all vaccine groups, with mild adverse events reported by 52.9% of participants, although serious adverse events were slightly more frequent in the IIV4 group (2.3%) compared to the IIV3 groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study. Treanor, JT., Albano, FR., Sawlwin, DC., et al.[2022]

High-dose trivalent inactivated influenza vaccine (HD-IIV3) and recombinant trivalent influenza vaccine (RIV) may improve vaccine effectiveness in adults aged 50-64 who are at high risk for influenza complications, suggesting a potential public health benefit.

The analysis indicates that using HD-IIV3 or RIV for high-risk patients could be a cost-effective strategy, with the HD-IIV3 & SD-IIV4 strategy costing $71,500 per quality-adjusted life year (QALY) gained, highlighting the economic viability of these vaccines in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults. Raviotta, JM., Smith, KJ., DePasse, J., et al.[2018]

High-dose inactivated trivalent influenza vaccine (HD-IIV3) provides significantly better protection against influenza-like illness and reduces hospital admissions in adults aged 65 and older compared to standard-dose vaccines, with a relative vaccine efficacy (rVE) of 19.5% for ILI and 9.1% for all-cause hospital admissions.

The study, which meta-analyzed data from seven studies involving a total of 992 screened studies, suggests that HD-IIV3 is more effective in preventing severe outcomes related to influenza, including pneumonia and cardiorespiratory events, indicating it should be considered for routine vaccination in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis. Lee, JKH., Lam, GKL., Shin, T., et al.[2023]

In a study involving over 2 million older adults during the 2018-19 and 2019-20 influenza seasons, the adjuvanted trivalent inactivated influenza vaccine (aIIV3) was found to be significantly more effective than the standard quadrivalent inactivated vaccine (IIV4e) in preventing both cardiorespiratory and respiratory diseases.

The use of aIIV3 resulted in substantial cost savings from hospitalizations, amounting to $392 million for cardiorespiratory issues and $145 million for respiratory issues in the 2018-19 season, highlighting both clinical efficacy and economic benefits for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical and economic assessment of adjuvanted trivalent versus standard egg-derived quadrivalent influenza vaccines among older adults in the United States during the 2018-19 and 2019-20 influenza seasons. Levin, MJ., Divino, V., Postma, MJ., et al.[2023]

In a study involving 757 adults aged 65 and older, the safety profile of the trivalent adjuvanted inactivated influenza vaccine (aIIV3) was found to be noninferior to that of the trivalent high-dose inactivated influenza vaccine (HD-IIV3), with similar rates of moderate-to-severe injection-site pain and other reactions.

Both vaccines did not show significant differences in health-related quality of life (HRQOL) changes post-vaccination, indicating that either vaccine is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. Schmader, KE., Liu, CK., Harrington, T., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05832307

The INFLUENTIAL Trial- Evaluation of National Inpatient ... This study plans to learn more about whether a stakeholder-informed, standardized inpatient vaccination program will increase influenza vaccination rates of ...

2. cdc.gov cdc.gov/flu-vaccines-work/php/effectiveness-studies/index.html

CDC Seasonal Flu Vaccine Effectiveness Studies **2020-2021 flu vaccine effectiveness was not estimated due to low influenza virus circulation during the 2020-2021 flu season.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718019/

Incremental benefit of high dose compared to standard ... The relative Vaccine effectiveness (rVE) for laboratory-confirmed influenza was 24% (95% CI:10–37%). Accordingly, the US Centers for Disease ...

4. academic.oup.com academic.oup.com/cid/article/81/3/667/7916523

Influenza Vaccine Effectiveness Against Hospitalizations and ... Among adults, 25% (11 632/46 614) of cases versus 44% (97 811/220 992) of controls across care settings had received vaccination. VE was 58% (95 ...

5. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-03955-w

a nationwide study using target trial emulation framework Having an influenza vaccination significantly reduced risks of influenza-associated death by 30%, various respiratory by 12–26%, cardiovascular complications ...

6. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7432a2.htm

Prevention and Control of Seasonal Influenza with Vaccines This report summarizes updates to the 2024–25 recommendations for use of seasonal influenza vaccines in the United States for the 2025–26 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5861790/

Influenza vaccines: Evaluation of the safety profile - PMC The relative risk of narcolepsy was 5- to 14-fold higher in children/adolescents and 2- to 7-fold higher in adults in the first year following immunization.

8. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2838476

High-Dose vs Standard-Dose Influenza Vaccine and ... Conclusions and Relevance This study found reduced incidence of cardiorespiratory hospitalization among those who received HD-IIV vs SD-IIV, ...

9. medrxiv.org medrxiv.org/content/10.1101/2025.01.03.25319959v1.full-text

Safety Monitoring of Health Outcomes following Influenza ... This study assessed the safety of 2023-2024 influenza vaccines among elderly US Medicare beneficiaries.