Clinical trial NCT01335087: Continuous Positive Airway Pressure (CPAP) in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Obstructive Sleep Apnea
Keywords: sleep apnea
secondary prevention
cardiovascular endpoint
Lead sponsor: Sociedad Española de Neumología y Cirugía Torácica
Sponsor class: OTHER
Collaborators: name: ResMed
name: Fondo de Investigacion Sanitaria
name: EsteveTeijin Healthcare
name: Spanish Society of Cardiology
name: Sociedad Madrileña de Neumologia
First posted: 2011-04-14
Enrollment: 1864
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of cardiovascular events in patients with acute coronary syndrome and co-occurring sleep apnea.
timeFrame: 12 month after the inclusion of the last patient
Secondary outcomes:
measure: Prevalence of OSA in patients who have suffered an episode of ACS.
timeFrame: 24 month (inclusion period)
measure: Composite of major CV events
timeFrame: 12 month after the inclusion of the last patient
measure: Components of primary composite endpoints separately.
timeFrame: 12 month after the inclusion of the last patient
measure: Number of re-vascularization procedures.
timeFrame: 12 month after the inclusion of the last patient
measure: All-cause mortality.
timeFrame: 12 month after the inclusion of the last patient
measure: New onset of ECG-confirmed atrial fibrillation or other arrhythmias.
timeFrame: 12 month after the inclusion of the last patient
measure: Newly diagnosed diabetes mellitus, according to standard definitions.
timeFrame: 12 month after the inclusion of the last patient
measure: Epworth Sleepiness Scale (ESS) and Test EuroQol (EQ-5D).
timeFrame: 12 month after the inclusion of the last patient
measure: Severity and phenotype of patients with OSA and clinical outcomes of ACS.
timeFrame: 12 month after the inclusion of the last patient
measure: CPAP compliance and CV events incidence.
timeFrame: 12 month after the inclusion of the last patient
measure: Biological risk markers related to mechanisms involved in cardiovascular complications in these patients.
timeFrame: 12 month after the inclusion of the last patient
measure: Cost-effectiveness analysis (Qualys) of the diagnosis and CPAP treatment of patients with ACS who have obstructive sleep apnea.
timeFrame: 12 month after the inclusion of the last patient
Other outcomes:
Locations:
city: Barcelone
country: Spain
facility: Spanish Respiratory Society
Study officials:
affiliation: Spanish Respiratory Sociey
name: Ferran Barbe, MD
role: PRINCIPAL_INVESTIGATOR
References:
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