Trial Outcomes & Findings for 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 (NCT NCT04137887)

Last Updated: 2025-09-17

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

33096 participants

Primary outcome timeframe

From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Results posted on

2025-09-17

Participant Flow

Study was conducted at a single site in Finland by Finnish Institute for Health and Welfare in collaboration with multiple health stations overseen by public health care centers in Finland. A total of 33096 participants were enrolled, out of which 1 participant withdrew consent prior to randomization. 33093 participants were vaccinated between 04 November 2019 and 23 December 2019. Among these, 16549 participants were vaccinated in the QIV-HD group and 16544 participants in the QIV-SD group.

Study was planned to be conducted over a period of 3 influenza seasons beginning in 2019-2020. Enrollment \& data collection were disrupted during the 2020-2021 \& 2021-2022 influenza seasons due to worldwide coronavirus disease 2019 (COVID-19). Data collection period was chosen as: from 14 days post-vaccination up to end of May of year following vaccination. Study was terminated prematurely after only 1 influenza season (2019-2020) \& thus included only season 2019-2020 assessment.

Participant milestones

Participant milestones
Measure	Group 1: 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 Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0.
Overall Study STARTED	16549	16546
Overall Study Vaccinated	16549	16544
Overall Study COMPLETED	16445	16450
Overall Study NOT COMPLETED	104	96

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: 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 Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0.
Overall Study Death	102	92
Overall Study Withdrawal by Subject	2	3
Overall Study Randomized but not treated	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.	Total n=33093 Participants Total of all reporting groups
Age, Continuous	72.6 years STANDARD_DEVIATION 5.7 • n=16549 Participants	72.5 years STANDARD_DEVIATION 5.6 • n=16544 Participants	72.5 years STANDARD_DEVIATION 5.6 • n=33093 Participants
Sex: Female, Male Female	8273 Participants n=16549 Participants	8241 Participants n=16544 Participants	16514 Participants n=33093 Participants
Sex: Female, Male Male	8276 Participants n=16549 Participants	8303 Participants n=16544 Participants	16579 Participants n=33093 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases	257 Participants	272 Participants

PRIMARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Primary Discharge Diagnoses For Any Respiratory and Circulatory Systems Diseases Hospitalizations Any diseases of the respiratory system	88 Participants	93 Participants
Number of Participants With Primary Discharge Diagnoses For Any Respiratory and Circulatory Systems Diseases Hospitalizations Any diseases of the circulatory system	171 Participants	184 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Pneumonia	62 Participants	62 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Heart failure	27 Participants	27 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Acute myocardial infarction	31 Participants	40 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Atrial fibrillation and flutter	40 Participants	32 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Cerebral infarction	27 Participants	28 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Influenza and pneumonia	62 Participants	62 Participants
Number of Participants With Primary Discharge Diagnoses for Various Respiratory and Circulatory Diseases Influenza	6 Participants	8 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Deaths Death due to Influenza	0 Participants	0 Participants
Number of Participants With Deaths Death (All-cause)	102 Participants	92 Participants
Number of Participants With Deaths Death due to any diseases of respiratory system	3 Participants	9 Participants
Number of Participants With Deaths Death due to any diseases of circulatory system	19 Participants	16 Participants
Number of Participants With Deaths Death due to Pneumonia	3 Participants	9 Participants
Number of Participants With Deaths Death due to Heart failure	3 Participants	1 Participants
Number of Participants With Deaths Death due to Acute myocardial infarction	0 Participants	4 Participants
Number of Participants With Deaths Death due to Atrial fibrillation and flutter	0 Participants	0 Participants
Number of Participants With Deaths Death due to Cerebral infarction	1 Participants	1 Participants
Number of Participants With Deaths Death due to Influenza and pneumonia	3 Participants	9 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Any diseases of the respiratory system	102 Participants	110 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Any diseases of the circulatory system	195 Participants	199 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Pneumonia	69 Participants	72 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Heart failure	45 Participants	43 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Acute myocardial infarction	27 Participants	37 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Atrial fibrillation and flutter	60 Participants	51 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Cerebral infarction	22 Participants	34 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Influenza and pneumonia	69 Participants	72 Participants
Number of Participants With Primary and Secondary Admission Diagnoses for Respiratory and Circulatory Diseases Influenza	7 Participants	7 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Any diseases of the respiratory system	130 Participants	143 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Any diseases of the circulatory system	257 Participants	263 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Pneumonia	72 Participants	78 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Heart failure	46 Participants	57 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Acute myocardial infarction	38 Participants	41 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Atrial fibrillation and flutter	105 Participants	99 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Cerebral infarction	29 Participants	34 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Influenza and pneumonia	72 Participants	78 Participants
Number of Participants With Primary and Secondary Discharge Diagnoses for Respiratory and Circulatory Diseases Influenza	9 Participants	9 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Hospital Emergency Room Visits Heart failure	15 Participants	11 Participants
Number of Participants With Hospital Emergency Room Visits Any diseases of the respiratory system	95 Participants	97 Participants
Number of Participants With Hospital Emergency Room Visits Any diseases of the circulatory system	158 Participants	158 Participants
Number of Participants With Hospital Emergency Room Visits Pneumonia	28 Participants	36 Participants
Number of Participants With Hospital Emergency Room Visits Acute myocardial infarction	0 Participants	0 Participants
Number of Participants With Hospital Emergency Room Visits Atrial fibrillation and flutter	109 Participants	118 Participants
Number of Participants With Hospital Emergency Room Visits Cerebral infarction	1 Participants	0 Participants
Number of Participants With Hospital Emergency Room Visits Influenza and pneumonia	28 Participants	36 Participants
Number of Participants With Hospital Emergency Room Visits Influenza	5 Participants	10 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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).

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Acute Primary Care Visits to Physician Pneumonia	23 Participants	25 Participants
Number of Participants With Acute Primary Care Visits to Physician Heart failure	16 Participants	19 Participants
Number of Participants With Acute Primary Care Visits to Physician Any diseases of the respiratory system	279 Participants	285 Participants
Number of Participants With Acute Primary Care Visits to Physician Any diseases of the circulatory system	137 Participants	120 Participants
Number of Participants With Acute Primary Care Visits to Physician Acute myocardial infarction	3 Participants	5 Participants
Number of Participants With Acute Primary Care Visits to Physician Atrial fibrillation and flutter	63 Participants	53 Participants
Number of Participants With Acute Primary Care Visits to Physician Cerebral infarction	2 Participants	2 Participants
Number of Participants With Acute Primary Care Visits to Physician Influenza and pneumonia	23 Participants	25 Participants
Number of Participants With Acute Primary Care Visits to Physician Influenza	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Major Acute Cardiovascular Events (MACE) Ischaemic heart diseases	46 Participants	68 Participants
Number of Participants With Major Acute Cardiovascular Events (MACE) Myocardial infarction	31 Participants	40 Participants
Number of Participants With Major Acute Cardiovascular Events (MACE) Unstable angina	16 Participants	30 Participants
Number of Participants With Major Acute Cardiovascular Events (MACE) Cerebral infarction	27 Participants	28 Participants

SECONDARY outcome

Timeframe: 14 to 30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days and 121 days or above

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Percentage of Observed Cardiorespiratory Events During the Assessment Period 61 to 90 days	17.20 percentage of events	20.49 percentage of events
Percentage of Observed Cardiorespiratory Events During the Assessment Period 91 to 120 days	19.93 percentage of events	18.65 percentage of events
Percentage of Observed Cardiorespiratory Events During the Assessment Period 121 days or above	32.12 percentage of events	31.22 percentage of events
Percentage of Observed Cardiorespiratory Events During the Assessment Period 14 to 30 days	11.83 percentage of events	10.20 percentage of events
Percentage of Observed Cardiorespiratory Events During the Assessment Period 31 to 60 days	18.93 percentage of events	19.44 percentage of events

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants. Here 'overall number of participants analyzed'= participants with available data for this OM.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=257 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=272 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Duration of Cardiorespiratory Hospitalization	5.0 days Interval 2.0 to 84.0	5.0 days Interval 2.0 to 60.0

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 65 to 74 years: Diseases of respiratory system	42 Participants	48 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 85 years and above: Diseases of circulatory system	26 Participants	18 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 65 to 74 years: Any diseases of respiratory/circulatory system	120 Participants	151 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 65 to 74 years: Diseases of circulatory system	78 Participants	105 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 75 years and above: Any diseases of respiratory/circulatory system	137 Participants	121 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 75 years and above: Diseases of respiratory system	46 Participants	45 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 75 years and above: Diseases of circulatory system	93 Participants	79 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 85 years and above: Any diseases of respiratory/circulatory system	32 Participants	32 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: By Age Groups 85 years and above: Diseases of respiratory system	6 Participants	15 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Any diseases of respiratory/circulatory system with comorbidity diabetes	60 Participants	63 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of circulatory system with comorbidity diabetes	34 Participants	44 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of respiratory system with comorbidity diabetes	26 Participants	21 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of respiratory system with comorbidity of chronic lung disease	28 Participants	37 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Any diseases of respiratory/circulatory system with comorbidity of cardiovascular history	104 Participants	108 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of respiratory system with comorbidity of cardiovascular history	27 Participants	28 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Any diseases of respiratory/circulatory system with comorbidity of chronic lung disease	54 Participants	57 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of circulatory system with comorbidity of chronic lung disease	26 Participants	21 Participants
Number of Participants With Hospitalizations Due to Cardiovascular or Respiratory Diseases: Groups With Specific Comorbidities Diseases of circulatory system with comorbidity of cardiovascular history	77 Participants	82 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Data for this outcome measure was not collected and analyzed as influenza epidemic period was not observed before study termination.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs) SAE	109 Participants	98 Participants
Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs) AESI	4 Participants	6 Participants
Number of Participants With Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Adverse Event of Special Interest (AESIs) SAR	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From 14 days post-vaccination up to 31 May 2020 post-vaccination (i.e., up to a duration of 6 months post-vaccination)

Population: Analysis was performed on all vaccinated participants.

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.

Outcome measures

Outcome measures
Measure	Group 1: QIV-HD n=16549 Participants Participants received a single injection of 0.7 mL QIV-HD, IM at Day 0.	Group 2: QIV-SD n=16544 Participants Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Number of Participants With Non-fatal SAEs	2 Participants	0 Participants

Adverse Events

Group1: QIV-HD

Serious events: 109 serious events

Other events: 0 other events

Deaths: 102 deaths

Group 2: QIV-SD

Serious events: 98 serious events

Other events: 0 other events

Deaths: 92 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Trial Transparency Team

Sanofi Pasteur

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Publication restrictions are in place

Restriction type: OTHER