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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02831608




Registration number
NCT02831608
Ethics application status
Date submitted
7/07/2016
Date registered
13/07/2016
Date last updated
22/09/2021

Titles & IDs
Public title
Study on the Effect of Influenza Vaccination After Heart Attack on Future Cardiovascular Prognosis
Scientific title
Influenza Vaccination After Myocardial Infarction (IAMI Trial): A Multicenter, Prospective, Randomized Controlled Clinical Trial Based on National Angiography and Angioplasty Registries
Secondary ID [1] 0 0
IAMI Trial
Secondary ID [2] 0 0
IAMI-2014
Universal Trial Number (UTN)
Trial acronym
IAMI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myocardial Infarction 0 0
Influenza, Human 0 0
Influenza Vaccines 0 0
Heart Failure 0 0
Stroke 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Drug: influenza vaccine - Standard influenza vaccine administered as a deep subcutaneous injection at one occasion per subject.

Placebo comparator: Drug: placebo - Saline administered as a deep subcutaneous injection at one occasion per subject.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of participants with death, a new myocardial infarction or stent thrombosis (first occurring) according to ICD-10 codes.
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
The number of participants with stroke/transient ischemic attack according to ICD-10 codes.
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
The number of participants with hospitalization for heart failure according to ICD-10 codes.
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Length of hospital stay per participant.
Timepoint [3] 0 0
Pertains only to hospital stay at baseline. Realistic time frame: till 2 weeks
Secondary outcome [4] 0 0
The number of participants with: cardiovascular death, a new myocardial infarction or stent thrombosis assessed separately for each diagnosis according ICD-10 codes.
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
The number of participants with: cardiovascular death according to ICD-10 codes.
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
The number of participants with a new revascularization
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
The number of participants with: death according to ICD-10 codes.
Timepoint [7] 0 0
1 year
Secondary outcome [8] 0 0
The number of participants with: a new myocardial infarction according to ICD-10 codes.
Timepoint [8] 0 0
1 year
Secondary outcome [9] 0 0
The number of participants with: stent thrombosis.
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
The number of participants with: arrhythmia according to ICD-10 codes.
Timepoint [10] 0 0
1 year

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2021
Sample size
Target
Accrual to date
Final
2571
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Blacktown Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Bangladesh
State/province [1] 0 0
Dhaka
Country [2] 0 0
Czechia
State/province [2] 0 0
Brno
Country [3] 0 0
Czechia
State/province [3] 0 0
Praha
Country [4] 0 0
Denmark
State/province [4] 0 0
Aalborg
Country [5] 0 0
Denmark
State/province [5] 0 0
Aarhus
Country [6] 0 0
Denmark
State/province [6] 0 0
Copenhagen
Country [7] 0 0
Denmark
State/province [7] 0 0
Odense
Country [8] 0 0
Latvia
State/province [8] 0 0
Riga
Country [9] 0 0
Norway
State/province [9] 0 0
Oslo
Country [10] 0 0
Sweden
State/province [10] 0 0
Göteborg
Country [11] 0 0
Sweden
State/province [11] 0 0
Jönköping
Country [12] 0 0
Sweden
State/province [12] 0 0
Karlstad
Country [13] 0 0
Sweden
State/province [13] 0 0
Linköping
Country [14] 0 0
Sweden
State/province [14] 0 0
Lund
Country [15] 0 0
Sweden
State/province [15] 0 0
Stockholm
Country [16] 0 0
Sweden
State/province [16] 0 0
Umea
Country [17] 0 0
Sweden
State/province [17] 0 0
Uppsala
Country [18] 0 0
Sweden
State/province [18] 0 0
Västerås
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Fife
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Aberdeen
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Dundee
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Edinburgh
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow

Funding & Sponsors
Primary sponsor type
Other
Name
Ole Frobert, MD, PhD
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Swedish Heart Lung Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Sanofi Pasteur, a Sanofi Company
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Uppsala University
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Lytics
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT02831608
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02831608