Clinical trial NCT04137887: Study to Evaluate the Effectiveness of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Adults 65 Years of Age and Older
Official title: Relative Effectiveness of a High-Dose Quadrivalent Influenza Vaccine Versus a Standard-Dose Quadrivalent Influenza Vaccine in Subjects 65 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Influenza (Healthy Volunteers)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-10-24
Enrollment: 33096
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary Objective:

To demonstrate the superior relative effectiveness of QIV-HD as compared to QIV-SD among persons 65 years of age and older for the prevention of cardiovascular and/or respiratory hospitalizations.

Secondary Objective:

* To assess the clinical relative effectiveness of QIV-HD as compared to QIV-SD in prevention of:
* inpatient hospitalization for selected circulatory and respiratory causes
* death, either all-cause or cardiovascular or respiratory causes
* inpatient hospitalization (using primary and secondary discharge diagnoses)
* inpatient hospitalization (using admission diagnoses)
* hospital emergency room visits
* primary care visits to physician or
* major acute cardiovascular events (MACE)
* To assess the characteristics of inpatient hospitalization or hospital emergency room visits or primary care visits to physician by QIV-HD and QIV-SD groups.
* To describe the clinical relative effectiveness of QIV-HD as compared to QIV-SD:
* by age group and by group with specific comorbidities
* for different periods of observation
* To describe all serious adverse events (SAEs) (including adverse event of special interest \[AESIs\]) for all subjects in both QIV-HD and QIV-SD groups.

Detailed description: Study duration per participant was 1 day of screening and vaccination. The study was planned to be conducted over a period of 3 influenza seasons beginning in 2019-2020. The vaccination period was from October to December.

Eligibility criteria: Inclusion criteria:

- Aged 65 years or older on the day of inclusion ("65 years" means from the day of the 65th birthday).

Exclusion criteria:

* Participation at the time of study enrollment (or in the 4 weeks \[28 days\] preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
* Previous vaccination against influenza (in the preceding 6 months) with either the study vaccines or another vaccine.
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Primary Discharge Diagnoses For Any Respiratory and Circulatory Systems Diseases Hospitalizations
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Secondary outcomes:
measure: Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Deaths
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Hospital Emergency Room Visits
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Acute Primary Care Visits to Physician
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Major Acute Cardiovascular Events (MACE)
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Percentage of Observed Cardiorespiratory Events During the Assessment Period
timeFrame: 14 to 30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days and 121 days or above
measure: Duration of Cardiorespiratory Hospitalization
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Occurrences for Cardiorespiratory Diseases During Influenza Epidemic Period
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs)
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
measure: Number of Participants With Non-fatal SAEs
timeFrame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Investigational Site Number 2469999
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Hollingsworth R, Palmu A, Pepin S, Dupuy M, Shrestha A, Jokinen J, Syrjanen R, Nealon J, Samson S, De Bruijn I. Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: Rationale and design of a real-world pragmatic randomized clinical trial. Am Heart J. 2021 Jul;237:54-61. doi: 10.1016/j.ahj.2021.03.007. Epub 2021 Mar 13.