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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Sociedad Española de Neumología y Cirugía Torácica.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
ResMed
Fondo de Investigacion Sanitaria
Esteve-Teijin
Fundacion RESPIRA
Societat Catalana de Cardiologia
Sociedad Madrileña de Neumologia
Information provided by:
Sociedad Española de Neumología y Cirugía Torácica
ClinicalTrials.gov Identifier:
NCT01335087
First received: April 5, 2011
Last updated: January 19, 2012
Last verified: April 2011
  Purpose

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.

Condition Intervention Phase
Acute Coronary Syndrome
Obstructive Sleep Apnea
Other: Standard care
Device: continuous positive airway pressure
Other: Reference
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Sociedad Española de Neumología y Cirugía Torácica:

Primary Outcome Measures:
  • Rate of cardiovascular events (cardiovascular death, non-fatal AMI, non-fatal stroke, hospital admission for heart failure, and new hospitalization for unstable angina or TIA) in patients with acute coronary syndrome and co-occurring sleep apnea. [ Time Frame: Twelve month after the inclusion of the last patient ] [ Designated as safety issue: No ]
    Cardiovascular events are: cardiovascular death, non-fatal AMI, non-fatal stroke, hospital admission for heart failure, and new hospitalization for unstable angina or TIA.


Secondary Outcome Measures:
  • Prevalence of OSA in patients who have suffered an episode of ACS. [ Time Frame: 24 month (inclusion period) ] [ Designated as safety issue: No ]
    Determined at the inclusion of the patient

  • Composite of CV death, myocardial infarction (MI) and ischaemic stroke. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • Components of primary composite endpoints separately (cardiovascular death, non-fatal AMI, non-fatal stroke, hospital admission for heart failure, and new hospitalization for unstable angina and TIA). [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • Number of re-vascularization procedures. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • All-cause mortality. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • New onset of ECG-confirmed atrial fibrillation or other arrhythmias. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • Newly diagnosed diabetes mellitus, according to standard definitions. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • OSA symptoms (Epworth Sleepiness Scale (ESS)) and quality of life ((Test EuroQol (EQ-5D). [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • Severity and phenotype of patients with OSA and clinical outcomes of ACS. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • CPAP compliance and CV events incidence. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • Biological risk markers related to mechanisms involved in cardiovascular complications in these patients. [ Time Frame: 12 month after the inclusion of the last patient ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1864
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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.
Other: Reference
Patients with an AHI < 15 h-1 (Group 3): This group will be followed according to standard care of cardiovascular risk factors and cardiovascular protocols and will be evaluated as a reference group. The inclusion of patients in this group be stratified by their AIH. We aim to include 50% of subject with an AHI < 15 h-1 and 50% of patients with an AHI > 15 h-1.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01335087

Contacts
Contact: Ferran Barbe, MD 34609328019 fbarbe@arnau.scs.es
Contact: Cristina Esquinas, RN 34658865112 crise04@hotmail.com

Locations
Spain
Spanish Respiratory Society Recruiting
Barcelone, Spain, 08009
Contact: Ferran Barbe, MD    34609328019    fbarbe@arnau.scs.es   
Principal Investigator: Ferran Barbe, MD         
Sub-Investigator: Manuel Sanchez-de-la-Torre, PhD         
Sponsors and Collaborators
Sociedad Española de Neumología y Cirugía Torácica
ResMed
Fondo de Investigacion Sanitaria
Esteve-Teijin
Fundacion RESPIRA
Societat Catalana de Cardiologia
Sociedad Madrileña de Neumologia
Investigators
Principal Investigator: Ferran Barbe, MD Spanish Respiratory Sociey
  More Information

No publications provided by Sociedad Española de Neumología y Cirugía Torácica

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ferran Barbe, Spanish Respiratory Society
ClinicalTrials.gov Identifier: NCT01335087     History of Changes
Other Study ID Numbers: PI10/02763
Study First Received: April 5, 2011
Last Updated: January 19, 2012
Health Authority: Spain: Ministry of Health

Keywords provided by Sociedad Española de Neumología y Cirugía Torácica:
sleep apnea
secondary prevention
cardiovascular endpoint

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Sleep Disorders, Intrinsic
Sleep Disorders
Acute Coronary Syndrome
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Dyssomnias
Nervous System Diseases
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain

ClinicalTrials.gov processed this record on April 17, 2014