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

NCT04137887 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: QHD000122019-001401-25U1111-1217-2654
• Study Type: interventional
• Target: 33,096
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza (Healthy Volunteers)

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  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

  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

  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

  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

  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

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

Study Arms (2)

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.

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.

Biological: Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD)

Interventions

Quadrivalent Influenza Vaccine (split virion, inactivated) High-Dose (QIV-HD) BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular

Also known as: Efluelda®

Group 1: QIV-HD

Standard-Dose Inactivated Influenza Vaccine Quadrivalent, Northern Hemisphere strains (QIV-SD) BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular

Also known as: VaxigripTetra®

Group 2: QIV-SD

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Investigational Site Number 2469999

Tampere, 33520, Finland

Location

Related Publications (2)

• 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.

  PMID: 38569647 DERIVED

• 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.

  PMID: 33722585 DERIVED

Related Links

• QHD00012 Plain Language Results Summary

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

COVID-19 severely impacted the study resulting in low influenza circulation and disruption of trial recruitment for subsequent seasons (no enrollment done for seasons 2020-21 \& 2021-22). Moreover, the events collected as primary outcomes could have been driven by COVID cases, diluting the effect of influenza vaccines on such events. The study was prematurely terminated.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double-blind: the participants, the outcome assessors in the hospitals and outpatient care, the Investigators, and the Sponsor will remain blinded to the vaccine assignment in order to avoid any bias in reporting and evaluating illnesses or SAEs. An unblinded qualified trial staff member will administer the appropriate vaccine.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2019
• First Posted: October 24, 2019
• Study Start: November 4, 2019
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: September 17, 2025
• Results First Posted: June 8, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

FI (1)