Vaccination Against Influenza to Prevent Cardiovascular Events After Acute Coronary Syndromes (VIP-ACS)

Evaluation of the Effectiveness of Double Dose Influenza Vaccination to Reduce Major Cardiovascular Events After an Acute Coronary Syndrome

Cardiovascular disease has a great burden in the context of public health, as well as the low pharmacological adherence of patients who have chronic non-transmissible diseases. However, the investigators do not have data on the efficacy of vaccination to reduce cardiovascular events in the acute coronary syndromes, and the few studies evaluating the cardioprotective potential of the influenza vaccine were conducted in countries with well defined seasonalities, divergent of Brazil, that presents a constant viral circulation during all months of the year and distinct among its regions. Therefore, study evaluating higher dose vaccination in a period that contemplates the seasonality of the influenza virus in Brazil may bring important findings to different scientific gaps, as well as clarify questions about the possible benefit of doubled vaccination - which does not present contraindications - immediately after a atherothrombotic event. If it shows real benefit, it could also be a future therapeutic tool adjuvant to traditional drug therapy in the prevention of cardiovascular events.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Biological: Double Dose Quadrivalent Influenza Vaccine; Biological: Standard Dose Quadrivalent Influenza Vaccine

Detailed Description

Phase III, randomized, controlled, multicenter, open-label, superiority, 1:1 allocation, blind assessment of clinical outcomes and intention-to-treat analysis clinical trial to determine whether increased doses(double dose) of influenza vaccine in the hospital phase, when compared to usual dose vaccination (30 days of randomization), decreases the risk of cardiovascular and respiratory events. Hospitalizations due to COVID-19 are excluded from the respiratory infection component of the primary outcome.

• Study Type: Interventional
• Enrollment (Actual): 1801
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Instituto Dante Pazzanese
  • Bahia
    • Ipiaú, Bahia, Brazil
      • Hospital e Clínica São Roque
    • Salvador, Bahia, Brazil
      • Hospital Ana Nery
    • Salvador, Bahia, Brazil
      • Hospital Cardio Pulmonar
  • Ceará
    • Fortaleza, Ceará, Brazil
      • Universidade Federal do Ceará / Hospital Universitário Walter Cantídio
  • DF
    • Brasilia, DF, Brazil
      • Instituto de Cardiologia do Distrito Federal
  • MG
    • Poços De Caldas, MG, Brazil
      • Hospital Santa Lucía
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil
      • Hospital Universitário Ciencias Medicas
  • PE
    • Recife, PE, Brazil
      • Pronto Socorro Cardiologico de Pernambuco
  • Paraná
    • Londrina, Paraná, Brazil
      • Hospital Universitário da Universidade Estadual de Londrina
  • Pernambuco
    • Recife, Pernambuco, Brazil
      • Hospital Agamenon Magalhaes
  • RJ
    • Rio De Janeiro, RJ, Brazil
      • Instituto Estadual De Cardiologia Aloysio De Castro
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital de Clínicas de Porto Alegre
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Hospital São Lucas da PUCRS
  • SP
    • Botucatu, SP, Brazil
      • Faculdade de Medicina de Botucatu - UNESP
    • Marília, SP, Brazil
      • Irmandade da Santa Casa de Misericórdia de Marília
    • São Paulo, SP, Brazil
      • Instituto do Coração - HC FMUSP
  • Santa Catarina
    • Itajaí, Santa Catarina, Brazil
      • IPEMI - Instituto de Pesquisas Médicas de Itajaí
    • Joinville, Santa Catarina, Brazil
      • Hospital Dona Helena
    • Joinville, Santa Catarina, Brazil
      • Hospital Regional Hans Dieter Schmidt
  • Sergipe
    • Aracaju, Sergipe, Brazil
      • Centro de Pesquisa Clinica do Coracao
  • São Paulo
    • Presidente Prudente, São Paulo, Brazil
      • Santa Casa de Misericórdia de Presidente Prudente

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age >= 18 years and older
• Acute coronary syndrome in hospital phase.

Exclusion Criteria:

• Participation in another clinical trial with vaccines;
• Refusal to provide consent;
• Hypersensitivity and/or anaphylaxis to any component of the vaccine, or Guillain-Barré within 6 weeks after previous influenza vaccine;
• Have already received the influenza vaccine with the same strains used in the study within the last 12 months of inclusion in the study
• Breastfeeding women;
• Pregnant women;
• Presenting an acute coronary syndrome during months of December, January, and February.
• Acute coronary syndrome hospitalization >7 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double Dose Quadrivalent Influenza Vaccine; Double Dose QIV during index ACS hospitalization	Biological: Double Dose Quadrivalent Influenza Vaccine; Double Dose QIV (30µg Hemagglutinin)
Active Comparator: Standard Dose Quadrivalent Influenza Vaccine; Standard Dose QIV 30 days after randomization	Biological: Standard Dose Quadrivalent Influenza Vaccine; Standard Dose QIV (15µg Hemagglutinin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite endpoint consisting of death, myocardial infarction, stroke, unstable angina hospitalization, heart failure hospitalization, urgent coronary revascularization or respiratory infections hospitalizations	The primary objective will be analyzed using the win ratio approach comparing every participant of treatment group to every participant of control group to determine a winner	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary End Point is a hierarchical outcome consisting only of cardiovascular death, myocardial infarction or stroke.	The key secondary end point will be analyzed using the win ratio approach comparing every participant of treatment group to every participant of control group to determine a winner	12 months
Total mortality	Time to first occurrence of all cause death	12 months
Cardiovascular mortality	Time to first occurrence of CV death	12 months
Myocardial infarction	Time to first occurrence of myocardial infarction	12 months
Unstable angina hospitalization	Time to first occurrence of Unstable angina hospitalization	12 months
Stroke	Time to first occurrence of stroke	12 months
TIA (Transient ischemic attack)	Time to first occurrence of TIA	12 months
Heart failure hospitalizations	Time to first occurrence of Heart failure hospitalizations	12 months
Respiratory infections hospitalizations	Time to first occurrence of hospitalization due to upper and lower respiratory tract infection (excluding COVID-19)	12 months
Need for myocardial revascularization	Time to first occurrence of urgent coronary revascularization ischemia guide (urgent or not-urgent)	12 months
Stent thrombosis	Time to first occurrence of probable and definite stent thrombosis	12 months
COVID-19 hospitalizations	Time to first occurrence of COVID-19 hospitalizations	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited injection site and systemic events, unsolicited adverse events and serious adverse events following vaccination.	Occurrence of solicited injection site (Pain, Erythema, Swelling, Induration, and Bruising) and systemic reactions (Fever, Headache, Malaise, Myalgia, and Shivering) will be assessed in all participants.	Day 0 up to Day 7 post-vaccination
Safety overview after influenza vaccination until the end of the study.	Occurrence of unsolicited adverse events, including serious adverse events.	12 months

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Ministry of Health, Brazil
• Investigators: Study Chair: Otávio Berwanger, MD-PhD, Academic Research Organization -- Hospital Israelita Albert Einstein; Principal Investigator: Henrique A Fonseca, PhD, Academic Research Organization -- Hospital Israelita Albert Einstein

Publications and helpful links

General Publications

• Fonseca HAR, Furtado RHM, Zimerman A, Lemos PA, Franken M, Monfardini F, Pedrosa RP, Patriota RLS, Passos LCS, Dall'Orto FTC, Hoffmann Filho CR, Nascimento BR, Baldissera FA, Pereira CAC, Caramori PRA, de Andrade PB, Esteves C, Salim EF, da Silva JH, Pedro IC, Silva MCR, de Pedri EH, Carioca ACRD, de Piano LPA, Albuquerque CSN, Moia DDF, Momesso RGRAP, Machado FP, Damiani LP, Soares RVP, Schettino GP, Rizzo LV, Nicolau JC, Berwanger O. Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial. Eur Heart J. 2022 Nov 1;43(41):4378-4388. doi: 10.1093/eurheartj/ehac472.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Actual): August 28, 2022
• Study Completion (Actual): August 28, 2022

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Actual): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Unstable angina; Non-ST-Elevation Myocardial Infarction - NSTEMI; ST-Elevation Myocardial Infarction - STEMI; Quadrivalent Influenza Vaccine - QIV
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Disease; Orthomyxoviridae Infections; Syndrome; Influenza, Human; Acute Coronary Syndrome; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VIP-ACS trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No