Beta Blocker Interruption After Uncomplicated Myocardial Infarction (AβYSS)

• ClinicalTrials.gov Identifier: NCT03498066
• Recruitment Status: Completed
• First Posted: April 13, 2018
• Last Update Posted: December 6, 2023
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Groupe Hospitalier Pitie-Salpetriere
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: March 21, 2018
• First Posted Date: April 13, 2018
• Last Update Posted Date: December 6, 2023
• Actual Study Start Date: August 29, 2018
• Actual Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 27, 2023)

The composite of Major Adverse Cardiovascular Events (MACE) [ Time Frame: Through study completion, with a minimum of 1 year ]

Will be evaluated with one-year minimum follow-up and will be the composite of Major Adverse Cardiovascular Events (MACE) including:

• All-cause death
• Myocardial infarction (MI)
• Stroke
• Hospitalisation for any cardiovascular (CV) reason.

Original Primary Outcome Measures (submitted: April 6, 2018)

The composite of Major Adverse Cardiovascular Events (MACE) [ Time Frame: up to 48 months ]

including: All-cause death Stroke Myocardial infarction Hospitalisation for other cardiovascular (CV) reason

Current Secondary Outcome Measures (submitted: November 30, 2023)

Quality of life [ Time Frame: Through study completion, with a minimum of 1 year ]

will be evaluated by the questionnaire EQ5D-5L Score (0 to 1) and EQ5D-5L Scale (0 to 100) with higher scores indicating a better quality of Life.

Original Secondary Outcome Measures (submitted: April 6, 2018)

• All individual parameters of MACE [ Time Frame: up to 48 months ]
  All cause death

  • Heart Failure
  • Arythmia = Ventricular or Supra-Ventricular Tachycardia
  • Syncope, Conduction disorders or PaceMaker Implantation
  • High Blood Pressure
• Stroke [ Time Frame: up to 48 months ]
  Stroke
• Myocardial Infarction (MI) (Classified by type of MI, including Stent Thrombosis) [ Time Frame: up to 48 months ]
  Myocardial Infarction (MI) (Classified by type of MI, including Stent Thrombosis)
• Hospitalisation for other CV reason [ Time Frame: up to 48 months ]
  Angina, Recurrent ischemia, Coronary Angiography or Coronary; Revascularisation outside of the scope of an MI; Heart Failure; Arythmia = Ventricular or Supra-Ventricular Tachycardia; Syncope, Conduction disorders or PaceMaker Implantation; High Blood Pressure;

Current Other Pre-specified Outcome Measures (submitted: November 27, 2023)

• Anxiety and Depression [ Time Frame: Through study completion, with a minimum of 1 year ]
  will be evaluated by using the HADS questionnaire to detect the presence of depression and anxiety ( there is no score; this will be determined by the response selected by the patient with "no" = no discomfort to "a lot" = significant discomfort
• Erection Dysfunction [ Time Frame: Through study completion, with a minimum of 1 year ]
  A precise evaluation of Erectile dysfunction will be proposed to male patients using an internationally validated questionnaire IIEF (International Index of Erectile Function) in French with 5 questions whose answer is graded from 0 to 5 per question
• Libido [ Time Frame: Through study completion, with a minimum of 1 year ]
  An evaluation of lack of sex drive will be evaluated by answering the following questions about the sexuality of the patient The frequency and degree of sex drive (self evaluation)
• Exercise Capacity [ Time Frame: Through study completion, with a minimum of 1 year ]
  will be evaluated by answering the following simple questions :

  • The weekly physical activity and the sport practiced
  • Participation in competitions or not additionally, the recording the results of stress tests when available
  • Pre- and post - inclusion stress/ Strain test data
• Side effects [ Time Frame: Through study completion, with a minimum of 1 year ]
  will be evaluated by answering the following questions: Presence of Blury Vision, Sensation of cold hands and feets, Insomnia and palpitations

Original Other Pre-specified Outcome Measures (submitted: April 6, 2018)

• Cardiovascular death [ Time Frame: up to 48 months ]
  Cardiovascular death
• Syncope/dizziness requiring a consultation or a hospitalisation. [ Time Frame: up to 48 months ]
  Syncope/dizziness requiring a consultation or a hospitalisation.
• Invasive procedures (catheterisation, percutaneous coronary intervention (PCI), pace-maker or automatic defibrillator implantation, endoscopy…) [ Time Frame: up to 48 months ]
  Invasive procedures (catheterisation, percutaneous coronary intervention
• Angina control [ Time Frame: up to 48 months ]
  Angina control
• Heart Rate Control (Cardiac Frequency during visit) [ Time Frame: first year only ]
  Heart Rate Control (Cardiac Frequency during visit)
• Blood Pressure Control (Blood pressure during visit) [ Time Frame: first year only ]
  Blood Pressure Control (Blood pressure during visit)
• An Episode of Heart failure (consultation or Hospitalisation) [ Time Frame: up to 48 months ]
  An Episode of Heart failure (consultation or Hospitalisation)
• The quality of life (QoL) [ Time Frame: up to 48 months ]
  The quality of life (QoL)
• The composite of: [ Time Frame: up to 48 months ]
  • Any Death and MI
  • CV death, MI, and stroke.
  • CV death, MI, and urgent coronary revascularisation.
  • CV death, MI, and recurrent ischemia requiring hospitalisation (with or without revascularisation).

Descriptive Information

• Brief Title: Beta Blocker Interruption After Uncomplicated Myocardial Infarction
• Official Title: Assessment of βeta Blocker Interruption After Uncomplicated mYocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization: The AβYSS Study
• Brief Summary: ABYSS is a national, multicenter, randomised, open label trial using the PROBE study design, that will evaluate the non-inferiority of the interruption of ΒB therapy after an uncomplicated MI after six months or more of follow-up compared to the continuation of βB evaluated by the primary endpoint or death, MI, Stroke and rehospitalization for others cardiovascular reasons.

Detailed Description

Despite the outstanding progress made in cardiac care over the last few years, cardiovascular diseases remain the leading cause of morbidity and mortality in developed countries.

After the initial clinical event, patients are considered to have a chronic disease which combined with the increasing actual life expectancy patients with CAD are a major source of expenses due to their life-long treatment and follow-up.

ΒB are prescribed during the initial hospitalisation for MI and in the post-MI phase. European (European Society of Cardiology, ESC) and American (ACC/AHA) guidelines initially gave βB therapy a class I recommendation for MI or acute coronary syndrome (ACS) for the first year of treatment and extended such recommendation without solid data up to 3 years after MI , . However, there has been no recent clinical trial to evaluate safety and efficacy of long term ΒB therapy in the contemporary therapeutic era. Taking such lack of evidence in account and acknowledging that clinical practice has changed, the latest ESC STEMI (2014) and NSTEMI (2015) Guidelines degraded the recommendation for the use of ΒB in post MI patients (Class IIa B) during the hospitalization period and they question the validity of its use after the initial stabilization phase. This was confirmed in the 2017 STEMI Guidelines.

The primary objective of the ABYSS trial is to demonstrate the non-inferiority of the interruption of ΒB therapy after an uncomplicated MI after six months or more of follow-up compared to the continuation of βB evaluated by the primary endpoint.

The primary endpoint of the study will be evaluated, with one-year minimum follow-up, and will be the composite of Major Adverse Cardiovascular Events (MACE) measured at the longest follow-up including:

• All-cause death
• Stroke
• Myocardial infarction Hospitalisation for other cardiovascular (CV) reason.

It is expected that the interruption of βB therapy will not alter the prognosis of patients and improve safety and quality of life of patients and considerably reduce healthcare direct or indirect costs.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Myocardial Infarction

Intervention

• Drug: Beta-blockers withdrawal
  withdrawal of all type of betablockers
• Drug: Continuation of the Betablockers (βB) treatment
  Use Betablockers treatment

Study Arms

• Experimental: Discontinuation of the Betablockers (βB)
  1850 post-MI patients treated with chronic βB treatment will undergo withdrawal of their βB treatment..
  Intervention: Drug: Beta-blockers withdrawal
• Active Comparator: Continuation of the Betablockers (βB)
  1850 post-MI patients treated with chronic βB treatment will be continued under their usual βB treatment without modification.
  Intervention: Drug: Continuation of the Betablockers (βB) treatment

• Publications *: Silvain J, Cayla G, Ferrari E, Range G, Puymirat E, Delarche N, Collet JP, Dumaine R, Slama M, Payot L, Kasty ME, Aacha K, Vicaut E, Montalescot G; ABYSS investigators of the ACTION Study Group,. betaeta blocker interruption after uncomplicated myocardial infarction: rationale and design of the randomized ABYSS trial. Am Heart J. 2023 Apr;258:168-176. doi: 10.1016/j.ahj.2023.01.014. Epub 2023 Jan 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2018): 3700
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 31, 2023
• Actual Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria

Subjects meeting all of the following criteria will be considered for enrolment into the study:

1. Male or female +/=18 years of age
2. Current treatment with βB whatever the drug or the dose used

3. Prior acute myocardial infarction 6 months or more before randomisation defined either by:

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   • An episode of ST elevation MI with ST segment elevation (STEMI) and/or the presence of Q wave (Type I MI)

   • an episode of Non ST Elevation MI (NSTEMI) with preferably at least one of the followings:

     • i) a documented hypokinetic or akinetic segment on echo or any other imaging technique
     • ii) segmental hypoperfusion Thallium or any other imaging technique
     • iii) segmental aspect of necrosis on MRI
   • An episode of silent MI discovered on ECG or Cardiac Imaging. Importantly = The mention of an MI on a report is enough to be considered as a prior MI and it is not necessary to retrieve the source document and/or documentation of this prior MI .
4. Patient affiliated to Social Security
5. Informed consent obtained in writing at enrolment into the study

Exclusion Criteria:

• Subjects presenting with any of the following will not be included in the study:

  1. Uncontrolled arterial hypertension according to investigator decision
  2. Prior episode of heart failure in the past two years of follow-up and/or low left ventricular ejection fraction <40% requiring the use of βB;
  3. New ACS (in the past 6 months) including UA/NSTEMI and STEMI;
  4. Persistent angina or ischemia (>10% viable myocardium) requiring the use of βB;
  5. Prior episode of ventricular or supraventricular arrhythmia in the past year of follow-up requiring the use of ΒB;
  6. Treatment with other investigational agents or devices within the previous 30 days, or previous enrolment in this trial.
  7. Pregnant Women or breast feeding women
  8. Patient under legal protection (protection of the court, or in curatorship or guardianship).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03498066
• Other Study ID Numbers: P150946J
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: There is not a plan to make IPD available

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Groupe Hospitalier Pitie-Salpetriere

Investigators

• Study Chair: Johanne SILVAIN, MD-PhD; APHP / Institut de Cardiologie, Pitié-Salpêtrière Hospital, Paris (APHP) / ACTION Study Group / Sorbonne Université Paris-France

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: November 2023