Influenza (Healthy Volunteers)Phase 3NCT04137887
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
A Phase 3 study testing Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD) and Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD) in people with Influenza (Healthy Volunteers), run by Sanofi Pasteur, a Sanofi Company at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza (Healthy Volunteers)
- What is being tested?
- Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD) and Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33,096 participants
- Where
- 1 siteFinland
- Study dates
- 4 Nov 2019to 31 May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Aged 65 years or older on the day of inclusion ("65 years" means from the day of the 65th birthday).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Influenza (Healthy Volunteers)
- Being tested
- Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD), Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD)Biological
Also called Efluelda®
Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular
Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)Biological
Also called VaxigripTetra®
Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular
| Study group | Role | What they receive |
|---|---|---|
| Group 1: QIV-HD | Experimental | Participants received a single injection of 0.7 milliliters (mL) high dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0. Receives: Biological: Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD) |
| Group 2: QIV-SD | Active comparator | Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0. Receives: Biological: Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases
Number of participants with hospitalizations due to any cardiovascular or respiratory diseases on the basis of International Classification of Diseases, Tenth Revision (ICD-10) codes as per health care professional (HCP) assessment were collected using Finnish health registers and reported in this outcome measure (OM). ICD-10 codes for respiratory system diseases: J00-J06 (acute upper respiratory infections), J09-J18 (influenza \& pneumonia), J20-J22 (other acute lower respiratory infections), J40-J47 (chronic lower respiratory diseases), J80-J81 (other respiratory diseases affecting interstitium), J85-J86 (suppurative \& necrotic conditions of lower respiratory tract); codes for circulatory diseases: I11 (hypertensive diseases), I20-I25 (ischemic heart diseases), I26-I27 (pulmonary heart disease \& diseases of pulmonary circulation), I30, I31, I33, I38-I42, I46-I50 (other forms of heart disease), I63-I67 (cerebrovascular diseases) \& I74 (diseases of arteries, arterioles \& capillaries).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Primary Discharge Diagnoses For Any Respiratory and Circulatory Systems Diseases Hospitalizations
Number of participants with primary discharge diagnoses (final diagnosis given to participant before release from hospital) for any respiratory \& circulatory diseases hospitalizations on the basis of ICD-10 codes per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for respiratory system diseases were: J00-J06 (acute upper respiratory infections), J09-J18 (influenza \& pneumonia), J20-J22 (other acute lower respiratory infections), J40-J47 (chronic lower respiratory diseases), J80-J81 (respiratory diseases affecting interstitium), J85-J86 (suppurative \& necrotic conditions of the lower respiratory tract); and codes for circulatory system diseases were: I11 (hypertensive diseases), I20-I25 (ischemic heart diseases), I26-I27 (pulmonary heart disease \& diseases of pulmonary circulation), I30, I31, I33, I38-I42, I46-I50 (other heart disease), I63-I67 (cerebrovascular diseases) and I74 (diseases of arteries, arterioles and capillaries).
Measured: 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 (14)
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases
Number of participants with primary discharge diagnoses (final diagnosis given to participant before release from hospital) due to each disease of respiratory and circulatory system on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. The codes selected were pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Deaths
Number of participants reporting death (all-cause) and due to any diseases of respiratory and circulatory system and separately due to each disease on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. Based on ICD-10 codes, codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85-J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. Codes for pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases
Number of participants with primary admission diagnosis (diagnosis given to the participant at the time of admission to hospital) and secondary admission diagnosis (diagnosis that coexist with the primary admission diagnosis at the time of admission) due to any diseases of respiratory and circulatory system and separately for each disease on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. Codes for pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases
Number of participants with primary discharge diagnosis (final diagnosis given to a participant before release from the hospital) and secondary discharge diagnosis (diagnoses that coexist with the primary discharge diagnosis at the time of discharge) due to any diseases of respiratory and circulatory system and separately for each disease on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. Codes for pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospital Emergency Room Visits
Number of participants reporting hospital emergency room visits due to any diseases of respiratory and circulatory system and separately due to each disease, on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. Codes for pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Acute Primary Care Visits to Physician
Number of participants reporting acute primary care visits to physician due to any diseases of the respiratory and circulatory system and separately for each disease, on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. Codes for pneumonia (J12-J18); heart failure (I50); acute myocardial infarction (I21); atrial fibrillation and flutter (I48); cerebral infarction (I63); influenza and pneumonia (J09-J18) and influenza (J09-J11).
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Major Acute Cardiovascular Events (MACE)
Major acute cardiovascular events (MACE) were defined by all of the following outcomes: ischemic heart diseases based on codes I20-I25, non-fatal myocardial infarction based on codes I21-I23, unstable angina based on codes I20 and I25 and fatal or non-fatal cerebral infarction based on code I63. Number of participants with MACE events on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and reported in this OM.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Percentage of Observed Cardiorespiratory Events During the Assessment Period
Percentage of observed cardiorespiratory events during the different time durations over the assessment period were reported in this OM. The following codes were taken into account: ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. International Classification of Primary Care Second Edition (ICPC-2) codes: R72, R74 to R81, R83, R95 and R96; K70, K74 to K80, K82, K84, K87 and K90 to K93.
Measured: 14 to 30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days and 121 days or above
Duration of Cardiorespiratory Hospitalization
Duration (in days) of cardiorespiratory hospitalization was defined as stop date of event (hospitalization) minus start date of event plus 1. The following codes were taken into account: ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups
Number of participants with hospitalizations due to any diseases of the respiratory or circulatory system and separately for respiratory and circulatory diseases on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and presented by age groups (65 to 74 years, 75 years and above and 85 years and above) in this OM. The following codes were taken into account: ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities
Number of participants with hospitalizations due to any diseases of the respiratory or circulatory system and separately for respiratory and circulatory diseases on the basis of ICD-10 codes as per HCP assessment were collected using Finnish health registers and presented by various comorbidities (diabetes, cardiovascular history and chronic lung disease) in this OM. The following codes were taken into account: ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85 and J86; and codes for any circulatory system diseases were: I11, I20-I25, I26, I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Occurrences for Cardiorespiratory Diseases During Influenza Epidemic Period
The influenza epidemic period as per Finnish epidemic thresholds was defined as the period where the influenza incidence was high. The following codes were taken into account: ICD-10 codes for any respiratory system diseases were: J00-J06, J09-J18, J20-J22, J40-J47, J80-J81, J85-J86; and codes for any circulatory system diseases were: I11 and I16, I20-I25, I26-I27, I30, I31, I33, I38-I42, I46-I50, I63-I67 and I74. ICPC-2 codes: R72, R74 to R81, R83, R95 and R96; K70, K74 to K80, K82, K84, K87 and K90 to K93.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs)
SAE: any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization/ prolongation of existing hospitalization, resulted in persistent/ significant disability/ incapacity, was congenital anomaly/ birth defect or was an important medical event. SAR: all noxious and unintended responses to study vaccine related to any dose administered that resulted in death, was life-threatening, required hospitalization/ prolongation of existing hospitalization, resulted in persistent/ significant disability/ incapacity, or was congenital anomaly or birth defect. SAR referred to potential causal relationship between study vaccine \& SAE, based on assessment of healthcare professional. AESI was defined as one of scientific \& medical concern specific to study for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was considered appropriate. Relatedness to study vaccine was based on Investigator's discretion.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Non-fatal SAEs
SAEs were defined as any untoward medical occurrence that at any dose was life-threatening, required inpatient hospitalization/ prolongation of existing hospitalization, resulted in persistent/ significant disability/ incapacity, was congenital anomaly/ birth defect or was an important medical event. Information on non-fatal SAEs was collected from the health registers.
Measured: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start4 Nov 2019
- Primary completion31 May 2020
- Study completion31 May 2020
Why it stopped: Enrollment terminated due to the COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Influenza (Healthy Volunteers)Studies of the same condition, open and under way.
- More trials run by Sanofi Pasteur, a Sanofi CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33,096 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi Pasteur, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi Pasteur, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04137887
- Sponsor's protocol ID
- QHD00012
- Other IDs
- 2019-001401-25, U1111-1217-2654, 2019
- Status last verified
- Sep 2025
- First submitted
- 11 Oct 2019
- Last updated
- 17 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
Palmu AA, Pepin S, Syrjanen RK, Mari K, Mallett Moore T, Jokinen J, Nieminen H, Kilpi T, Samson SI, De Bruijn I. High-Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults. Influenza Other Respir Viruses. 2024 Apr;18(4):e13270. doi: 10.1111/irv.13270.
PubMed 38569647Hollingsworth 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.
PubMed 33722585
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04137887
- Acronym / sponsor ID
- QHD00012
- Conditions
- Influenza (Healthy Volunteers)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment terminated due to the COVID-19 pandemic
- Enrolment
- 33,096 participants (actual)
- Lead sponsor
- Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 31 May 2020 (actual)
- Study completion
- 31 May 2020 (actual)
- First posted
- 24 Oct 2019 (actual)
- Results
- Posted 8 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: QIV-HD | Experimental | Biological: Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD)Participants received a single injection of 0.7 milliliters (mL) high dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0. |
| Group 2: QIV-SD | Active comparator | Biological: Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Aged 65 years or older on the day of inclusion ("65 years" means from the day of the 65th birthday).
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD)Also: Efluelda®Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular | Biological | Group 1: QIV-HD |
| Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)Also: VaxigripTetra®Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular | Biological | Group 2: QIV-SD |
Primary outcome
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of participants with hospitalizations due to any cardiovascular or respiratory diseases on the basis of International Classification of Diseases, Tenth Revision (ICD-10) codes as per health care professional (HCP) assessment were collected using Finnish health registers and reported in this outcome measure (OM). ICD-10 codes for respiratory system diseases: J00-J06 (acute upper respiratory infections), J09-J18 (influenza \& pneumonia), J20-J22 (other acute lower respiratory infections), J40-J47 (chronic lower respiratory diseases), J80-J81 (other respiratory diseases affecting interstitium), J85-J86 (suppurative \& necrotic conditions of lower respiratory tract); codes for circulatory diseases: I11 (hypertensive diseases), I20-I25 (ischemic heart diseases), I26-I27 (pulmonary heart disease \& diseases of pulmonary circulation), I30, I31, I33, I38-I42, I46-I50 (other forms of heart disease), I63-I67 (cerebrovascular diseases) \& I74 (diseases of arteries, arterioles \& capillaries).
Number of Participants With Primary Discharge Diagnoses For Any Respiratory and Circulatory Systems Diseases Hospitalizations
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of participants with primary discharge diagnoses (final diagnosis given to participant before release from hospital) for any respiratory \& circulatory diseases hospitalizations on the basis of ICD-10 codes per HCP assessment were collected using Finnish health registers and reported in this OM. ICD-10 codes for respiratory system diseases were: J00-J06 (acute upper respiratory infections), J09-J18 (influenza \& pneumonia), J20-J22 (other acute lower respiratory infections), J40-J47 (chronic lower respiratory diseases), J80-J81 (respiratory diseases affecting interstitium), J85-J86 (suppurative \& necrotic conditions of the lower respiratory tract); and codes for circulatory system diseases were: I11 (hypertensive diseases), I20-I25 (ischemic heart diseases), I26-I27 (pulmonary heart disease \& diseases of pulmonary circulation), I30, I31, I33, I38-I42, I46-I50 (other heart disease), I63-I67 (cerebrovascular diseases) and I74 (diseases of arteries, arterioles and capillaries).
14 secondary outcomes
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Deaths
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospital Emergency Room Visits
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Acute Primary Care Visits to Physician
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Major Acute Cardiovascular Events (MACE)
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Percentage of Observed Cardiorespiratory Events During the Assessment Period
Time frame: 14 to 30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days and 121 days or above
Duration of Cardiorespiratory Hospitalization
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Occurrences for Cardiorespiratory Diseases During Influenza Epidemic Period
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs)
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Number of Participants With Non-fatal SAEs
Time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38569647Palmu AA, Pepin S, Syrjanen RK, Mari K, Mallett Moore T, Jokinen J, Nieminen H, Kilpi T, Samson SI, De Bruijn I. High-Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults. Influenza Other Respir Viruses. 2024 Apr;18(4):e13270. doi: 10.1111/irv.13270.
- Derived from this study: PubMed 33722585Hollingsworth 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.
- QHD00012 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi Pasteur, a Sanofi Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD) and Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD) in people with Influenza (Healthy Volunteers), run by Sanofi Pasteur, a Sanofi Company at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases (time frame: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04137887, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.