Heart Failure, Hypertension, Pulmonary, Sleep Apnea, Obstructive
Conditions
Brief summary
The objective of the study is to evaluate the effect of continuous positive airway pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated heart failure (HF) patients with obstructive sleep apnea (OSA). The study will also assess changes in functional parameters, biomarkers, and echocardiographic parameters.
Detailed description
The ASAP-HF study is a prospective, randomized, controlled, two-center, study with a parallel group design, with subjects randomized to either control (no APAP) or active treatment (APAP) in a 1:1 ratio. Group A (active): standard medical therapy plus treatment with continuous APAP for 48hrs, or Group B (control): standard medical therapy only. Many people who have heart failure (HF) also have sleep-disordered breathing (SDB), which is breathing irregularities during sleep. These irregularities may interrupt the sleep as well as increase the rate of progression of Heart Failure. The ASAP-HF study is being done to see if certain clinical outcomes are improved in acute decompensated heart failure (HF) patients with SDB by using a non-invasive breathing device continuously for a short period of time (48 hours) while patient is still in the hospital. The device is called AirSense™ 10 AutoSet (AutoSet). It consists of an air flow generator, air tubing, an air humidifier, and a mask. As the patient breathe through the mask, the AutoSet monitors breathing. The primary objective of this pilot study is to evaluate the effect of continuous positive airway pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated heart failure (HF) patients with obstructive sleep apnea (OSA). The study will also assess changes in functional parameters, biomarkers, and echocardiographic parameters . This device is not currently used to diagnose sleep apnea and its utility is not well studied. This study will establish the utility of the device in diagnosing sleep apnea.
Interventions
DEVICEAirSense™ 10 AutoSet
The AirSense 10 AutoSet is a device that provide non-invasive ventilatory support to treat patients with sleep disordered breathing. The device is intended for home and hospital use. The treatment pressure required by the patient may vary due to changes in sleep state, body position and airway resistance. In AutoSet mode, the device provides only that amount of pressure required to maintain upper airway patency. The AirSense 10 AutoSet provides a minimum and maximum pressure within the range of 4-20 cm of water.
OTHERStandard Medical Therapy
Standard medical therapy according to current guidelines.
Sponsors
Albert Einstein Healthcare Network
Resmed Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
CPAP Device
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or more 2. Decompensated Congestive Heart Failure with systolic Pulmonary Artery pressures of ≥50 mmHg (including Right Atrial pressure) 3. Prior clinical diagnosis of heart failure 4. Moderate to Severe predominately obstructive sleep disordered breathing documented by polygraphy with Apnea Hypopnea Index (AHI) ≥20e/h and 5% of the time spent \<90% O2 Sat (minimum 2hr recording time) 5. Patient is able to fully understand study information and sign informed consent
Exclusion criteria
1. Chronic renal insufficiency (Hemodialysis or serum creatinine \> 2) 2. Hemodynamically significant valvular disease 3. Severe arthritis or inability to complete 6 Minute Walk Test 4. Left Ventricular Assist Device/ heart transplant or hemodynamically unstable 5. Patient taking any Pulmonary vasodilators, including home oxygen. 6. Known diagnosis of Obstructive Sleep Apnea (OSA) and on active therapy 7. 80% of the respiratory events being central/Cheyne-Stokes breathing 8. Recent cardiac surgery (within 30 days of admission) 9. Recent stroke (within 30 days of admission or with persistent neurological deficits) 10. Severe Chronic Obstructive Pulmonary Disease defined as forced expiratory volume at one second (FEV1) \< 50%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Artery Systolic Pressure. | 48 hours | The primary objective of this pilot study is to evaluate the effect of continuous positive airway pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated heart failure (HF) patients with severe obstructive sleep apnea (OSA). The study will also assess changes in functional parameters, biomarkers, and echocardiographic parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs | 48 hours | To compare changes in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) measured at baseline and compared to 48hrs after. |
| Length of Stay | 1 year | The total stay in the hospital during the admission will be measured by days. |
| Blood Oxygenation. | 48 hours | Changes in arterial blood oxygenation will be compared via arterial blood gas analysis performed at baseline and after 48h to assess arterial pressure of oxygen. |
| Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs | 48 hours | 6-minute walk tests were performed on admission and repeated after 48 hours from the initial. The walked distance was measured in meters. |
| Fluid Retention | 48 hours | Change in fluid retention as measured by weight at baseline and after 48 hours. |
| E/e' as an Assumption of LVEDP. | 48 hours | Measurement of E/e' in 2D echocardiography as an assumption of LVEDP and PV acceleration time comparing baseline and after 48hrs. |
| Heart Failure Symptoms | 48 hours | Heart failure symptoms as assessed by the New York Heart Association scale (NYHA) classification at baseline and after 48 hours. NYHA scale ranges from Class I to IV. Higher classes are associated with worst outcomes. Class I: No symptoms and no limitation in ordinary physical activity. Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity.Comfortable only at rest. Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. |
Countries
Germany, United States
Participant flow
Recruitment details
Subjects were recruited from the inpatient clinical services of the Albert Einstein Medical Center Philadelphia (US) and from the Heart and Diabetes Center of North Rhine-Westphalia (Germany). Patients signed an informed consent for the study prior to any study-related procedure. Before randomization, all eligibility criteria were confirmed.
Participants by arm
| Arm | Count |
|---|---|
| Group A Standard medical therapy plus AirSense™ 10 AutoSet for 48hrs.
AirSense™ 10 AutoSet: The AirSense 10 AutoSet is a device that provides non-invasive ventilatory support to treat patients with sleep-disordered breathing. The device is intended for home and hospital use. The treatment pressure required by the patient may vary due to changes in the sleep state, body position and airway resistance. In AutoSet mode, the device provides only that amount of pressure required to maintain upper airway patency. The AirSense 10 AutoSet provides a minimum and maximum pressure within the range of 4-20 cm of water. | 10 |
| Group B Standard medical therapy only.
Standard Medical Therapy: Standard medical therapy according to current guidelines. | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Group B | Group A | Total |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 9.96 | 70.6 years STANDARD_DEVIATION 11.5 | 67.75 years STANDARD_DEVIATION 10.8 |
| Apnea-hypopnea index (AHI) | 34.3 events/hour STANDARD_DEVIATION 9.2 | 31.7 events/hour STANDARD_DEVIATION 8 | 33.1 events/hour STANDARD_DEVIATION 8.5 |
| Body mass index (BMI) | 31.2 kg/m2 STANDARD_DEVIATION 4.2 | 28.7 kg/m2 STANDARD_DEVIATION 5.8 | 30.0 kg/m2 STANDARD_DEVIATION 5 |
| History of COPD Diagnosis of COPD confirmed with PFTs | 1 Participants | 4 Participants | 5 Participants |
| History of COPD No diagnosis of COPD or negative PFTs | 10 Participants | 6 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 12 Participants |
| Region of Enrollment Germany | 6 participants | 5 participants | 11 participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
| Smoking history Active smoker | 2 Participants | 1 Participants | 3 Participants |
| Smoking history Former smoker | 3 Participants | 3 Participants | 6 Participants |
| Smoking history Never smoker | 6 Participants | 6 Participants | 12 Participants |
| Type of heart failure according to EF (HFrEF/HFpEF) HFpEF | 3 Participants | 5 Participants | 8 Participants |
| Type of heart failure according to EF (HFrEF/HFpEF) HFrEF | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Pulmonary Artery Systolic Pressure.
The primary objective of this pilot study is to evaluate the effect of continuous positive airway pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated heart failure (HF) patients with severe obstructive sleep apnea (OSA). The study will also assess changes in functional parameters, biomarkers, and echocardiographic parameters.
Time frame: 48 hours
Population: Patients pulmonary artery systolic pressures were measured by transthoracic echocardiography (TTE) on admission and 48 hours after enrollment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Pulmonary Artery Systolic Pressure. | Baseline | 58.6 mmHg |
| Group A | Pulmonary Artery Systolic Pressure. | After 48 hours | 42.8 mmHg |
| Group B | Pulmonary Artery Systolic Pressure. | Baseline | 62.7 mmHg |
| Group B | Pulmonary Artery Systolic Pressure. | After 48 hours | 57.5 mmHg |
Secondary
Blood Oxygenation.
Changes in arterial blood oxygenation will be compared via arterial blood gas analysis performed at baseline and after 48h to assess arterial pressure of oxygen.
Time frame: 48 hours
Population: Data was not available for all participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Blood Oxygenation. | Baseline | 72.84 mmHg |
| Group A | Blood Oxygenation. | After 48 hours | 80 mmHg |
| Group B | Blood Oxygenation. | Baseline | 76.7 mmHg |
| Group B | Blood Oxygenation. | After 48 hours | 77.9 mmHg |
Secondary
E/e' as an Assumption of LVEDP.
Measurement of E/e' in 2D echocardiography as an assumption of LVEDP and PV acceleration time comparing baseline and after 48hrs.
Time frame: 48 hours
Population: Data was not available for all the subjects at baseline and 48 hours after. PI has left the institution; efforts to contact unsuccessful; clarifying data information not available
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | E/e' as an Assumption of LVEDP. | Baseline | 18.6 Ratio |
| Group A | E/e' as an Assumption of LVEDP. | After 48 hours | 14.8 Ratio |
| Group B | E/e' as an Assumption of LVEDP. | Baseline | 18.2 Ratio |
| Group B | E/e' as an Assumption of LVEDP. | After 48 hours | 16.5 Ratio |
Secondary
Fluid Retention
Change in fluid retention as measured by weight at baseline and after 48 hours.
Time frame: 48 hours
Population: Data after 48 hours was not available for the participants of the study. PI has left the institution; efforts to contact unsuccessful; data information not available for after 48hr time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Fluid Retention | Baseline | 82.6 Kg |
| Group B | Fluid Retention | Baseline | 94.7 Kg |
Secondary
Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs
6-minute walk tests were performed on admission and repeated after 48 hours from the initial. The walked distance was measured in meters.
Time frame: 48 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs | Baseline | 202.6 meters |
| Group A | Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs | After 48 hours | 222.6 meters |
| Group B | Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs | Baseline | 153.6 meters |
| Group B | Functional Parameters (6 Minute Walk Test) From Baseline to 48hrs | After 48 hours | 161.8 meters |
Secondary
Heart Failure Symptoms
Heart failure symptoms as assessed by the New York Heart Association scale (NYHA) classification at baseline and after 48 hours. NYHA scale ranges from Class I to IV. Higher classes are associated with worst outcomes. Class I: No symptoms and no limitation in ordinary physical activity. Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity.Comfortable only at rest. Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Time frame: 48 hours
Population: Data was not available for participants after 48 hours. PI has left the institution; efforts to contact unsuccessful; data information not available for after 48hr time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Heart Failure Symptoms | Baseline | 3.2 units on a scale |
| Group B | Heart Failure Symptoms | Baseline | 3.5 units on a scale |
Secondary
Length of Stay
The total stay in the hospital during the admission will be measured by days.
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group A | Length of Stay | 9.2 days |
| Group B | Length of Stay | 13.7 days |
Secondary
N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs
To compare changes in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) measured at baseline and compared to 48hrs after.
Time frame: 48 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs | Baseline | 1087.6 picogram/mililiter |
| Group A | N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs | After 48 hours | 466.5 picogram/mililiter |
| Group B | N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs | Baseline | 1532.7 picogram/mililiter |
| Group B | N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) From Baseline to 48hrs | After 48 hours | 1500.2 picogram/mililiter |
Post Hoc
Ejection Fraction in HFrEF
Calculated ejection fraction in patients with heart failure with reduced ejection fraction (\<45%) at baseline and after 48 hours.
Time frame: 48 hours
Population: Analyzing only patients with heart failure with reduced ejection fraction (\<45%).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group A | Ejection Fraction in HFrEF | After 48 hours | 30 percentage (%) |
| Group A | Ejection Fraction in HFrEF | Baseline | 23 percentage (%) |
| Group B | Ejection Fraction in HFrEF | After 48 hours | 26.7 percentage (%) |
| Group B | Ejection Fraction in HFrEF | Baseline | 26.8 percentage (%) |