Continuous Positive Airway Pressure (CPAP) in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC)

October 25, 2018 updated by: Ferran Barbe, Sociedad Española de Neumología y Cirugía Torácica

Impact of Sleep Apnea Syndrome in the Evolution of Acute Coronary Syndrome. Effect of Intervention With Continuous Positive Airway Pressure (CPAP). A Prospective Randomized Study. ISAACC Study

OSA may be a modifiable risk factor for cardiovascular disease due to its association with hypertension, stroke, heart attack and sudden death. The standard therapy for symptomatic OSA is continuous positive airway pressure (CPAP). CPAP has been shown to effectively reduce snoring, obstructive episodes and daytime sleepiness and to modestly reduce blood pressure and other risk factors for cardiovascular disease. The overall aim of ISAACC is to determine if CPAP can reduce the risk of heart attack, stroke or heart failure for people with OSA admitted in a hospital for an acute coronary syndrome.

Overall objective:

To assess the impact of obstructive sleep apnea (OSA) and its treatment on the clinical evolution of patients with acute coronary syndrome (ACS).

Primary objectives:

1. To determine if continuous positive airway pressure (CPAP) treatment will reduce the rate of cardiovascular events (cardiovascular (CV) death, non-fatal events (acute myocardial infarction (AMI), non-fatal stroke, hospital admission for heart failure, and new hospitalizations) for unstable angina or transient ischaemic attack (TIA)) in patients with ACS and co-occurring sleep apnea.

Secondary objectives:

  1. Determine the prevalence of OSA in patients who have suffered an episode of ACS.

  2. Other secondary objectives will include the effects of CPAP on:

    • To evaluate a composite of CV death, myocardial infarction (MI) and ischaemic stroke.
    • Components of primary composite endpoints
    • Re-vascularization procedures
    • To evaluate all-cause death
    • To evaluate new onset, ECG-confirmed atrial fibrillation or other arrhythmias
    • To evaluate newly diagnosed diabetes mellitus, according to standard definitions
    • To evaluate OSA symptoms (Epworth Sleepiness Scale (ESS))
    • To evaluate quality of life in patients with ACS (Test EuroQol (EQ-5D).
  3. To establish the relationship between the severity and phenotype of patients with OSA and clinical outcomes of ACS.
  4. To establish the relationship between CPAP compliance and CV events incidence.
  5. To identify biological risk markers that allow us to establish the most important mechanisms involved in cardiovascular complications in these patients.
  6. To conduct a cost-effectiveness analysis of the diagnosis and CPAP treatment of patients with ACS who have obstructive sleep apnea.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Methods:

Study design: multi-centre, open label, parallel, prospective, randomised, controlled trial.

Patients: We will include consecutive patients with an ACS diagnosis evaluated in participating Coronary Care Unit.

Study sites: IRB Lleida (Lleida), Hospital Son Dureta (Palma de Mallorca), Hospital Clínic (Barcelona), Hospital Germans Tries i Pujol (Barcelona), Hospital de Bellvitge (Barcelona), Hospital Sant Pau (Barcelona), Hospital Txagorritxu (Vitoria), Hospital de Cruces (Bilbao), Hospital San Pedro de Alcántara (Cáceres), Hospital Parc Taulí (Barcelona) and Hospital de Guadalajara (Guadalajara), Hospital de Vallecas (Madrid), Hospital de Yagüe (Burgos), Hospital de Requena (Valencia), Hospital San Juan, (Alicante), Hospital Central de Asturias (Oviedo).

Duration of the study: 3 years. Methodology: During a hospital stay we will assess the degree of daytime sleepiness (Epworth Scale) in patients treated at the Coronary Care Unit with a diagnosis of ACS. The results of this evaluation will define the inclusion of the patient in the study.

Patients with and ESS score ≤ 10 will be included in the study and will undergo a cardio-respiratory polygraphy. Patients with an AHI ≥ 15 h-1 will be randomized to CPAP treatment or conservative. Patients with and AHÍ < 15 h-1 will be followed as standard management according to cardiovascular protocols and will be evaluated as a reference group. Therefore, the study will have three groups, with a total of 1,864 patients, as follows: patients with an AHI ≥ 15 h-1 will be randomized to CPAP treatment (Group 1) (n=632) or conservative treatment (Group 2) (n=632). Patients with an AHI < 15 h-1 that will be followed as a reference group (Group 3) (n=600).

Patients with an ESS score higher than 10 will be excluded of the study and referred to the sleep unit of each participating center for evaluation.

Patients included in the study will be monitored and followed for a minimum of one year and a maximum of three years. Patients will be examined at the time of inclusion (T0), after one month (T1), three months (T2), six months (T3), 12 months (T4) and every six months thereafter, if applicable, during the follow-up period. Evaluations will include; i)new episodes of ACS, stroke, TIA, heart failure, hospitalization for cardiovascular causes and cardiovascular mortality, ii) biological risk markers involved in cardiovascular complications, iii) an evaluation of the cost-effectiveness of diagnosis and CPAP treatment in patients with ACS who have obstructive sleep apnea.

Study Type

Interventional

Enrollment (Actual)

1864

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelone, Spain, 08009
        • Spanish Respiratory Society

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Men and women over 18 years old.
  2. Patients admitted for documented symptoms of ACS with or without T segment elevation and have an hospital stay between 24h and 72 h in the moment to perform polygraphy .
  3. Patients with and Epworth Sleep Scale score ≤ 10 (patients without excessive daytime sleepiness).
  4. Written informed consent signed.

Exclusion Criteria:

  1. Previous CPAP treatment for OSA diagnosis
  2. Psycho-physical inability to complete questionnaires.
  3. Presence of any previously diagnosed sleep disorders: narcolepsy, insomnia, chronic sleep deprivation, regular use of hypnotic or sedative medications and restless leg syndrome
  4. Patients with > 50% of central apneas or the presence of Cheyne-Stokes Respiration (CSResp)
  5. Patients with chronic diseases: neoplasia, renal failure (GFR<30 ml/min), severe chronic obstructive pulmonary disease, chronic depression and other very limiting chronic diseases.
  6. A medical history that may interfere with the study objectives or, in the opinion of the investigator, compromise the conclusions.
  7. Any medical factor, social or geographical, that may jeopardize patient compliance.(e.g., alcohol consumption (more 80 gr/day in men and more than 60 gr / day in women), no fixed address, disorientation, or a history of non-compliance).
  8. Any process, cardiovascular or otherwise, that limits life expectancy to less than one year.
  9. Patients in cardiogenic shock who have poor expectations for short-term outcomes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lifestyle
Standard care for OSA: lifestyle, and sleep hygiene counselling
Other: Standard care
Patients with conservative treatment: (Group 2). This group will also be instructed in hygienic-dietary measures, standard care of cardiovascular risk factors and sleep hygiene counselling.
Experimental: Continuous positive airway pressure CPAP
CPAP treatment every night plus standard care for OSA: lifestyle, and sleep hygiene counselling
Other: Standard care
Patients with conservative treatment: (Group 2). This group will also be instructed in hygienic-dietary measures, standard care of cardiovascular risk factors and sleep hygiene counselling.
Device: continuous positive airway pressure
Patients with CPAP treatment (Group 1): CPAP pressure titration will be performed by automated equipment before discharge. It will follow the methodology described by our group (Mass et al. Alternative Methods of titrating continuous positive airway pressure: a large multicentre study. American Journal of Respiratory and Critical Care Medicine (2004) vol. 170 (11) pp. 1218-1224). This group will also be instructed in hygienic-dietary measures recommended for all patients, standard care of cardiovascular risk factors and sleep hygiene counselling.
No Intervention: Reference
This group will be followed according to cardiovascular protocols and will be evaluated as a reference group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of cardiovascular events in patients with acute coronary syndrome and co-occurring sleep apnea.
Time Frame: 12 month after the inclusion of the last patient
Cardiovascular events are: cardiovascular death, non-fatal AMI, non-fatal stroke, hospital admission for heart failure, and new hospitalization for unstable angina or TIA.
12 month after the inclusion of the last patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of OSA in patients who have suffered an episode of ACS.
Time Frame: 24 month (inclusion period)
Determined at the inclusion of the patient
24 month (inclusion period)
Composite of major CV events
Time Frame: 12 month after the inclusion of the last patient
CV death, myocardial infarction (MI) and ischaemic stroke.
12 month after the inclusion of the last patient
Components of primary composite endpoints separately.
Time Frame: 12 month after the inclusion of the last patient
Cardiovascular events are: cardiovascular death, non-fatal AMI, non-fatal stroke, hospital admission for heart failure, and new hospitalization for unstable angina or TIA.
12 month after the inclusion of the last patient
Number of re-vascularization procedures.
Time Frame: 12 month after the inclusion of the last patient
Revascularisation procedures, including PCI, CABG, peripheral arterial revascularisation and intra-cerebral stent insertion
12 month after the inclusion of the last patient
All-cause mortality.
Time Frame: 12 month after the inclusion of the last patient
All-cause mortality.
12 month after the inclusion of the last patient
New onset of ECG-confirmed atrial fibrillation or other arrhythmias.
Time Frame: 12 month after the inclusion of the last patient
ECGs were performed at baseline and during the follow-up period; ECG and medical records were collected tovconfirm a hospitalization for atrial fibrillation event
12 month after the inclusion of the last patient
Newly diagnosed diabetes mellitus, according to standard definitions.
Time Frame: 12 month after the inclusion of the last patient
Newly diagnosed diabetes mellitus, according to standard definitions
12 month after the inclusion of the last patient
Epworth Sleepiness Scale (ESS) and Test EuroQol (EQ-5D).
Time Frame: 12 month after the inclusion of the last patient
OSA symptoms: Epworth Sleepiness Scale (ESS). Quality of life: Test EuroQol (EQ-5D).
12 month after the inclusion of the last patient
Severity and phenotype of patients with OSA and clinical outcomes of ACS.
Time Frame: 12 month after the inclusion of the last patient
To establish the relationship between the severity and phenotype of patients with OSA and clinical outcomes of ACS.
12 month after the inclusion of the last patient
CPAP compliance and CV events incidence.
Time Frame: 12 month after the inclusion of the last patient
To establish the relationship between CPAP compliance and CV events incidence.
12 month after the inclusion of the last patient
Biological risk markers related to mechanisms involved in cardiovascular complications in these patients.
Time Frame: 12 month after the inclusion of the last patient
To identify biological risk markers that allow us to establish the most important mechanisms involved in cardiovascular complications in these patients.
12 month after the inclusion of the last patient
Cost-effectiveness analysis (Qualys) of the diagnosis and CPAP treatment of patients with ACS who have obstructive sleep apnea.
Time Frame: 12 month after the inclusion of the last patient
Cost-effectiveness analysis (Qualys) of the diagnosis and CPAP treatment of patients with ACS who have obstructive sleep apnea
12 month after the inclusion of the last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sociedad Española de Neumología y Cirugía Torácica

Collaborators

Fondo de Investigacion Sanitaria
ResMed
EsteveTeijin Healthcare
Societat Catalana de Cardiologia
Sociedad Madrileña de Neumologia

Investigators

  • Principal Investigator: Ferran Barbe, MD, Spanish Respiratory Sociey

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Actual)

September 1, 2018

Study Completion (Actual)

September 1, 2018

Study Registration Dates

First Submitted

April 5, 2011

First Submitted That Met QC Criteria

April 13, 2011

First Posted (Estimate)

April 14, 2011

Study Record Updates

Last Update Posted (Actual)

October 29, 2018

Last Update Submitted That Met QC Criteria

October 25, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI10/02763

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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