NCT02831608

Brief Summary

Background. For more than a century a causal link between influenza and cardiovascular disease has been suspected. It is conceivable that influenza may precipitate plaque rupture, increase cytokines with central roles in plaque destabilization and trigger the coagulation cascade. Accordingly, registry studies, case control studies and a few small randomized trials, all underpowered for clinical endpoints, have demonstrated that the risk for acute myocardial infarction (AMI) is increased following respiratory infection and that the risk of stroke and AMI in patients with established cardiovascular disease seem to be reduced following influenza vaccination. In May 2015 a Cochrane review concluded that influenza vaccination may reduce cardiovascular mortality and cardiovascular events but bias and inconsistent results in prior studies require higher-quality evidence to confirm these findings. High costs and little commercial interest in conducting a randomized trial on influenza vaccine in cardiovascular disease stand in the way. Objective. The objective is to document whether influenza vaccination protects against cardiovascular events and death in patients with an AMI or very high risk stable coronary artery disease patients. Methods. Population: 4400 patients with ST-elevation (STEMI), non-ST elevation myocardial infarction (NSTEMI) or very high risk stable coronary artery disease are randomized 1:1 in a blinded fashion using an RRCT design and followed up via registries and telephone calls. Intervention: Influenza vaccination. Control: Placebo (saline). Outcome: The primary endpoint is a composite of death, myocardial infarction and stent thrombosis till 1 year. Patients will be included in the study in all of Sweden's 7 university hospitals and 5 general hospitals, 4 university hospitals and 1 general hospital in Denmark, in 1 specialized heart center in Norway, 2 university hospitals in Czech Republic, 6 hospitals in Scotland, 1 university hospital in Latvia and 2 hospitals in Bangladesh. Secondary endpoints are time to all-cause death till 1 year, time to cardiovascular death till 1 year, time to stent thrombosis till 1 year, time to revascularization till 1 year, time to myocardial infarction till 1 year, time to cardiovascular death, a new myocardial infarction or stent thrombosis (first occurring) till 1 year, time to stroke, including TIA till 1 year, time to rehospitalization for heart failure till 1 year, time to hospitalization for arrhythmia till 1 year or length of hospital stay (if information is available). From a hypothesis generating perspective we aim to follow up patients through registries beyond 1 year and up to 5 years. The trial has been approved by the ethical committee system (Dnr 2014/264) and the Medical Products Agency (EudraCTnr -2014-001354-42) in Sweden. Perspectives. If a clinical benefit can be demonstrated in this prospective trial influenza vaccination may become an important novel in-hospital therapy for patients with cardiovascular disease and the accompanying direct and indirect societal gains will be profound.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,571

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Oct 2016

Longer than P75 for phase_4

Geographic Reach
8 countries

29 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 7, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

July 13, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

October 1, 2016

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2021

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2021

Completed
Last Updated

September 22, 2021

Status Verified

September 1, 2021

Enrollment Period

4.5 years

First QC Date

July 7, 2016

Last Update Submit

September 15, 2021

Conditions

Myocardial InfarctionInfluenza, HumanInfluenza VaccinesHeart FailureStroke

Outcome Measures

Primary Outcomes (1)

  • The number of participants with death, a new myocardial infarction or stent thrombosis (first occurring) according to ICD-10 codes.

    Composite endpoint of time to all-cause death, a new myocardial infarction or stent thrombosis (first occurring).

    1 year

Secondary Outcomes (10)

  • The number of participants with stroke/transient ischemic attack according to ICD-10 codes.

    1 year

  • The number of participants with hospitalization for heart failure according to ICD-10 codes.

    1 year

  • Length of hospital stay per participant.

    Pertains only to hospital stay at baseline. Realistic time frame: till 2 weeks

  • The number of participants with: cardiovascular death, a new myocardial infarction or stent thrombosis assessed separately for each diagnosis according ICD-10 codes.

    1 year

  • The number of participants with: cardiovascular death according to ICD-10 codes.

    1 year

  • +5 more secondary outcomes

Other Outcomes (1)

  • The primary and secondary outcomes assessed beyond 1 year

    5 years

Study Arms (2)

Drug: influenza vaccine

EXPERIMENTAL

Standard influenza vaccine administered as a deep subcutaneous injection at one occasion per subject.

Biological: Influenza vaccine

Drug: placebo

PLACEBO COMPARATOR

Saline administered as a deep subcutaneous injection at one occasion per subject.

Biological: Placebo

Interventions

Influenza vaccineBIOLOGICAL
Also known as: Vaxigrip, Vaxigrip Tetra
Drug: influenza vaccine
PlaceboBIOLOGICAL
Drug: placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with a diagnosis of ST-elevation myocardial infarction (STEMI) or
  • Patients with a diagnosis of non-STEMI or
  • Patients with stable coronary artery disease ≥75 years of age undergoing angiography/PCI AND with at least one additional risk criterion
  • and
  • A finalized coronary angiography/PCI (optional for sites in Bangladesh).
  • Male or female subjects ≥18 years.
  • Written informed consent.

You may not qualify if:

  • Influenza vaccination during the current influenza season or anticipating to be vaccinated during the current influenza season.
  • Indication for influenza vaccination for some indication other than myocardial infarction.
  • Severe allergy to eggs or previous allergic reaction to influence vaccine.
  • Suspicion of febrile illness or acute, ongoing infection.
  • Hypersensitivity to the active substances or ingredients of Vaxigrip or against any residues, such as eggs (ovalbumin or chicken proteins), neomycin, formaldehyde and octoxinol.
  • Subjects with endogenic or iatrogenic immunosuppression that may result in reduced immunization response.
  • Inability to provide informed consent.
  • Age below 18 years.
  • Previous randomization in the IAMI trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Blacktown Hospital

Sydney, New South Wales, Australia

Location

National Heart Foundation and Research Institute (NHFH)

Dhaka, Bangladesh

Location

National Institute of Cardiovascular Diseases (NICVD)

Dhaka, Bangladesh

Location

St. Anne University Hospital

Brno, Czechia

Location

University Hospital Kralovske Vinohrady

Prague, Czechia

Location

Aalborg University Hospital

Aalborg, Denmark

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Bispebjerg Hospital

Copenhagen, Denmark

Location

Rigshospitalet, University of Copenhagen

Copenhagen, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Pauls Stradins Clinical University Hospital

Riga, Latvia

Location

LHL-sykehuset Gardermoen

Oslo, Norway

Location

Sahlgrenska sjukhuset

Gothenburg, Sweden

Location

Jönköping Hospital

Jönköping, Sweden

Location

Karlstad Central Hospital

Karlstad, Sweden

Location

University Hospital Linkoping

Linköping, Sweden

Location

Skånes universitetssjukhus

Lund, Sweden

Location

Danderyds sjukhus

Stockholm, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Stockholm South General Hospital

Stockholm, Sweden

Location

University Hospital Umeå

Umeå, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Centrallasarettet

Västerås, Sweden

Location

Victoria Hospital

Kirkcaldy, Fife, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Royal Infirmary of Edinburg

Edinburgh, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, United Kingdom

Location

Hairmyres Hospital

Glasgow, United Kingdom

Location

Related Publications (3)

  • Clar C, Oseni Z, Flowers N, Keshtkar-Jahromi M, Rees K. Influenza vaccines for preventing cardiovascular disease. Cochrane Database Syst Rev. 2015 May 5;2015(5):CD005050. doi: 10.1002/14651858.CD005050.pub3.

    PMID: 25940444BACKGROUND

  • Frobert O, Gotberg M, Angeras O, Jonasson L, Erlinge D, Engstrom T, Persson J, Jensen SE, Omerovic E, James SK, Lagerqvist B, Nilsson J, Karegren A, Moer R, Yang C, Agus DB, Erglis A, Jensen LO, Jakobsen L, Christiansen EH, Pernow J. Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial. Am Heart J. 2017 Jul;189:94-102. doi: 10.1016/j.ahj.2017.04.003. Epub 2017 Apr 18.

    PMID: 28625387BACKGROUND

  • Frobert O, Gotberg M, Erlinge D, Akhtar Z, Christiansen EH, MacIntyre CR, Oldroyd KG, Motovska Z, Erglis A, Moer R, Hlinomaz O, Jakobsen L, Engstrom T, Jensen LO, Fallesen CO, Jensen SE, Angeras O, Calais F, Karegren A, Lauermann J, Mokhtari A, Nilsson J, Persson J, Stalby P, Islam AKMM, Rahman A, Malik F, Choudhury S, Collier T, Pocock SJ, Pernow J. Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Circulation. 2021 Nov 2;144(18):1476-1484. doi: 10.1161/CIRCULATIONAHA.121.057042. Epub 2021 Aug 30.

    PMID: 34459211RESULT

MeSH Terms

Conditions

Myocardial InfarctionInfluenza, HumanHeart FailureStroke

Interventions

Influenza Vaccinesvaxigrip

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisRespiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Viral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

July 7, 2016

First Posted

July 13, 2016

Study Start

October 1, 2016

Primary Completion

April 1, 2021

Study Completion

August 1, 2021

Last Updated

September 22, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will not share

Locations

AU(1)CZ(2)BA(2)LA(1)DK(5)NO(1)SE(11)GB(6)