PRedictOrs, PHEnotypes and Timing of Obstructive Sleep Apnea in Acute Coronary Syndrome

Sleep Clinical Trial

— PROPHET-ACS  

Official title:

PRedictOrs, PHEnotypes and Timing of Obstructive Sleep Apnea in Acute Coronary Syndrome (PROPHET-ACS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04002739
• Other study ID #: 2589
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2019
• Est. completion date: December 15, 2019

Study information

• Verified date: August 2019
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: Pier-Valerio Mari, MD
• Phone: (+39) 3313881904
• Email: piervalerio.mari[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obstructive Sleep Apnea (OSA) is a well-known disorder of upper airways collapse during sleep time leading to oxygen desaturation and sleep fragmentation. Despite being increasingly recognized as cardiovascular risk, the effect of OSA on clinical outcomes after Acute Coronary Syndrome (ACS) is not fully defined. Also, OSA syndrome is highly prevalent in ACS and may be related to the deterioration of cardiac function resulting in worsening of the severity of sleep apnea or the intermittent hypoxia could be cardio-protective via the ischemic preconditioning event. Serial sleep studies have shown the progressive reduction of the Apnea / Hypopnea Index (AHI) from the admission in Coronary Care Unit (CCU) to 6 weeks, 12 weeks and 6-month follow up, making necessary to re-assess the severity of OSA after discharge. Therefore, further research in this field is necessary to screen and predict those ACS patients who may experience a change in their AHI index over time.

Description:

Obstructive Sleep Apnea (OSA) is a well-known disorder of upper airways collapse during sleep time leading to oxygen desaturation, sleep fragmentation, tissue suffering and hypercapnia. The repeated airways collapse leads to a fall of blood saturation levels during sleep time and it is linked to daytime sleepiness, road traffic accidents, cognitive deficits, depression, myocardial infarction, pulmonary hypertension and stroke.

Despite being increasingly recognized as a major cardiovascular risk, the effect of OSA on clinical outcomes after Coronary Artery Disease (CAD) is not fully defined. The presentation of Acute Coronary Syndrome (ACS) can be unstable angina, non-ST Elevation Myocardial Infarction (NSTEMI) or ST-Elevation Myocardial Infarction (STEMI). Sleep apnea prevalence in the context of acute coronary syndromes (ACS) is sizeable, varying from 36.9%-82% when polysomnography is executed briefly after admission in Cardiovascular Care Unit (CCU). The high prevalence of OSA in ACS may be related to the deterioration of cardiac function resulting in worsening of the severity of sleep apnea. In converse, OSA has also been proposed as a protective factor in CAD. The intermittent hypoxia related to OSA could have a cardio-protective role during acute ACS via the phenomenon of "ischemic preconditioning", showing that in acute MI patients higher AHI was associated with lower peak troponin-T levels in partially and fully adjusted models.

Furthermore, the improvement of cardiac outcomes at the follow-up post-discharge seems to positively influence the severity of OSA. In particular, serial sleep studies have interestingly shown a progressive reduction of the AHI at 6 weeks, 12 weeks and 6-month follow up, making necessary to re-assess the severity of OSA after discharge. Therefore, further research in this field is necessary to screen and predict those ACS patients with a diagnosis of OSA made at admission in CCU who may experience a change in their AHI index over time, in order to identify those with a potential unfavourable prognosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 15, 2019
• Est. primary completion date: September 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Subjects with a diagnosis of ACS (STEMI or NSTEMI) admitted to CCU of our institution within 72 hours from Myocardial Infarct (MI)

• Age between 18 and 85 years old

Exclusion Criteria:

• Previous diagnosis of OSA or ongoing CPAP treatment

• Chronic/Home Oxygen therapy

• Cardiogenic shock

• Heart failure exacerbation

• use of mechanical ventilation

• Active use of benzodiazepines

• Pregnancy or breastfeeding

• Unable to sign the informed consent

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Infarction
• Myocardial Infarction
• NSTEMI - Non-ST Segment Elevation MI
• Sleep
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Sleep-Disordered Breathing
• ST Elevated Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Diagnostic Test:
• Polygraphy
Patients will perform polygraphy during the CCU stay (baseline) and, if found to have a diagnosis of Obstructive Sleep Apnea (OSA) syndrome, will complete the study with a follow-up visit at 90-day (follow-up). Diagnosis of OSA syndrome will require an Apnea / Hypopnea Index (AHI) more than 5 events per hour.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution of Obstructive Sleep Apnea severity in Acute Coronary Syndrome	Change of Obstructive Sleep Apnea (OSA) severity from baseline to 90 days in patients affected by an Acute Coronary Syndrome (ACS). Within 72 hours from admission, patients will perform a polygraphy and the Apnea / Hypopnea Index (AHI) will be determined. OSA syndrome is defined by AHI more than 5.0 per hour and can be mild (AHI between 5.0 and 15), moderate (AHI between 15.0 and 30.0) or severe (AHI more than 30.0).; When a diagnosis of OSA is confirmed, the patient will have a follow up visit with a new polygraphy and AHI will be defined again. Patients are not going to receive any treatment for the sleep-disorder breathing between baseline and 90-day. The difference between AHI baseline and AHI of the follow-up will define the evolution of OSA severity and will show an improved, stable or worsened sleep-disorder.	Baseline, 90 days
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Coronary	Culprit vessel as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Echocardiography	Ejection fraction (EF) and Systolic Pulmonary Artery Pressure (SPAP) as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline, 90 days
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - EKG Holter	Arrhythmias, mean heart rate, SDNN, r-MSSD, pNN50%, Mean Log LF/HF as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Bioelectrical impedance	Resistance and reactance as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline, 90 days
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - ESS	Epworth Sleepiness Scale (ESS) as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The primary statistic of interest will be the effect size.	Baseline, 90 days
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - STOP-BANG	STOP-BANG as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The test is a baseline screening evaluation of Obstructive Sleep Apnea (OSA) diagnosis. A score <3 is not predictive of OSA while a final result =3 is suggestive of OSA. The primary statistic of interest will be the effect size.	Baseline, 90 days
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Mallampati Score	Mallampati Score as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography.; It is a baseline evaluation of the back of a patient's throat by asking the patient to open the mouth and extend the tongue. The anatomy of the oral cavity is visualized; specifically, the assessor notes whether the base of the uvula, faucial pillars and soft palate are visible.; A Mallampati Score =2 is not predictive of OSA while a final result <3 is suggestive of OSA.; The primary statistic of interest will be the effect size.	Baseline
Secondary	Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Serological domain	Blood samples result such as CK, Creatin kinase, Glucose, Cholesterol, nt-proBNP, CRP, Creatinin as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography.	Baseline
Secondary	Prevalence of Obstructive Sleep Apnea (OSA)	Prevalence expressed as the number of events per hour of the sleep apneas due to obstructive cause in patients with a diagnosis of Obstructive Sleep Apnea (OSA) Syndrome assessed with polysomnography. Obstructive Sleep Apnea will be defined as an Obstructive Apnea Index per hour more than 5.0/h in polysomnography.	Baseline, 90 days
Secondary	Evolution of Obstructive Sleep Apnea Syndrome	The change of the Obstructive Apnea Index (expressed as the number of events per hour) from the baseline to the 90-day evaluation.	Baseline, 90 days
Secondary	Prevalence of Central Sleep Apnea (CSA)	Prevalence expressed as the number of events per hour of the sleep apneas due to central cause in patients with a diagnosis of Obstructive Sleep Apnea (OSA) Syndrome assessed with polysomnography. Central Sleep Apnea will be defined as a Central Apnea Index per hour more than 5.0/h in polysomnography.	Baseline, 90 days
Secondary	Evolution of Central Sleep Apnea (CSA)	The change of the Central Apnea Index (expressed as the number of events per hour) from the baseline to the 90-day evaluation.	Baseline, 90 days
Secondary	Culprit vessel	Evaluate the baseline prevalence of the culprit vessel responsible for Acute Coronary Syndrome (ACS). Culprit's vessels are one or more of the following: Left Anterior Descending Artery; Circumflex artery; Right Coronary Artery	Baseline
Secondary	Blood samples characteristics	Evaluate the baseline prevalence and the potential correlation in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of serological biomarkers such as: Troponins, creatinkinase, Creatinin, nt-proBNP, C reactive protein, Glucose, Cholesterol.	Baseline
Secondary	Bioelectrical impedance characteristics	Evaluate the baseline prevalence and the changing after 90 days in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of bioelectrical impedance, in particular, reactance and impedance.	Baseline, 90 days
Secondary	Evaluation of Ejection Fraction	Ejection fraction (EF) is a measurement made by echocardiography and expressed as a percentage that describes how much blood the left ventricle pumps out with each contraction. Evaluation of EF will be performed in baseline and after 90 days with echocardiography.; The EF is classified as: EF=55%: Normal EF 40%	Baseline, 90 days
Secondary	Evaluation of Systolic Pulmonary Artery Pressure (SPAP)	The Systolic Pulmonary Artery Pressure (SPAP) is an echocardiographic value expressed as mercury millimetres (mmHg) that describes the likelihood of the presence of Pulmonary Hypertension (PH). Evaluation of Systolic Pulmonary Artery Pressure (SPAP) will be performed in baseline and after 90 days with echocardiography.; The SPAP is classified as: SPAP=35 mmHg: Normal 35mmHg	Baseline, 90 days
Secondary	Evolution of Ejection Fraction	Ejection fraction (EF) is a measurement made by echocardiography and expressed as a percentage that describes how much blood the left ventricle pumps out with each contraction. The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a change of at least 8% of the EF baseline value.	Baseline, 90 days
Secondary	Evolution of Systolic Pulmonary Artery Pressure (SPAP)	The Systolic Pulmonary Artery Pressure (SPAP) is an echocardiographic value expressed as mercury millimetres (mmHg) that describes the likelihood of the presence of Pulmonary Hypertension (PH). The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a change of at least 5mmHg from the SPAP baseline value.	Baseline, 90 days
Secondary	Polysomnographic characteristics	Within 72 hours from admission in Coronary Care Unit (CCU), patients will perform a polygraphy and the Apnea / Hypopnea Index (AHI) will be determined. OSA syndrome is defined by AHI more than 5.0 per hour and can be mild (AHI between 5.0 and 15), moderate (AHI between 15.0 and 30.0) or severe (AHI more than 30.0). When a diagnosis of OSA is confirmed, the patient will have a follow up visit with a new polygraphy and AHI will be defined again.	Baseline, 90 days
Secondary	Evaluation of daytime sleepiness	Assessment of sleepiness status using the questionnaire "Epworth Sleepiness Score" (ESS). The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. A result in ESS score more than 10 is suggestive for daytime sleepiness.	Baseline, 90 days
Secondary	Evolution of daytime sleepiness	Change from baseline to 90 days of the questionnaire "Epworth Sleepiness Score" (ESS). The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a reduction of at least 2 points of the baseline value.	Baseline, 90 days
Secondary	Baseline screening of Obstructive Sleep Apnea	Baseline screening evaluation of Obstructive Sleep Apnea (OSA) diagnosis using the validated questionnaire "STOP-BANG". A score <3 is not predictive of OSA while a final result =3 is suggestive of OSA.	Baseline, 90 days
Secondary	Baseline prediction of Obstructive Sleep Apnea	Baseline evaluation of the back of a patient's throat by asking the patient to open the mouth and extend the tongue. The anatomy of the oral cavity is visualized; specifically, the assessor notes whether the base of the uvula, faucial pillars and soft palate are visible. Four classes can be distinguished: Class I: Soft palate, uvula, fauces, pillars visible. Class II: Soft palate, major part of uvula, fauces visible. Class III: Soft palate, base of uvula visible. Class IV: Only hard palate visible. A Mallampati Score =2 is not predictive of OSA while a final result <3 is suggestive of OSA.	Baseline
Secondary	24 hours-EKG Holter baseline characteristics	Evaluate the baseline prevalence and the potential correlation in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of 24 hours EKG Holter using values such as: arrhythmias, mean heart rate, SDNN, r-MSSD, pNN50%, Mean Log LF/HF.	Baseline

External Links

•   "Determinants and evolution of obstructive sleep apnea syndrome after myocardial infarction". The sample size of the trial PROPHET-ACS was derived from this pilot study presented as abstract at the European Sleep and Breathing Conference 2019, Marseille.