E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cheyne-Stokes Respiration in chronic heart failure |
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E.1.1.1 | Medical condition in easily understood language |
Sleep apnea in heart failure |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In a proof-of concept-Study we therefore aim to test the hypothesis that high flow therapy attenuates hypoxemic burden in patients with heart failure with reduced ejection fraction.
Primary study endpoint:
Reduction of hypoxemic burden >50% compared to baseline using HFT versus sham-HFT
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E.2.2 | Secondary objectives of the trial |
Changes in parameters regarding sleep, hemodynamics and cardiorespiratory function compared to baseline using HFT versus sham-HFT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18-90 years
• New York Heart Association (NYHA) class II to IV
• Left ventricular ejection fraction ≤ 45%
• Predominantly central sleep apnea (AHI ≥15 events per hour, with >80% central events [apnea or hypopnea] and a central AHI of ≥10 events per hour)
• Hypoxemic burden ≥ 25%
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E.4 | Principal exclusion criteria |
• daytime hypercapnia (pCO2 > 45 mmHg)
• ongoing ventilation therapy
• cardiothoracic surgery within the last 3 months
• myocardial infarction within the last 6 months
• unstable angina
• acute myocarditis
• stroke within the last 3 months
• epilepsy, known cerebral damage, dementia
• untreated restless-legs-syndrome
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of hypoxemic burden >50% compared to baseline using HFT versus sham-HFT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Changes in parameters listed below compared to baseline using HFT versus sham-HFT:
time in bed, min
total sleep time, min
sleep latency, min
latency to S3, min
S1 stadium/total sleep time, %
S2 stadium/total sleep time, %
S3 stadium/total sleep time, %
REM sleep/total sleep time, %
arousals/total sleep time, n
respiratory arousals/total sleep time, n
desaturation arousals/total sleep time, n
average systolic blood pressure, mmHg
average diastolic blood pressure, mmHg
longest apnoea, s
longest hypopnoea, s
obstructive apnoea, h-1
mixed apnoea, h-1
central apnoea, h-1
obstructive hypopnoea, h-1
central hypopnoea, h-1
apnoea+hypopnoea total, h-1
desaturations, h-1
mean sO2, %
lowest sO2, %
mean desaturation, %
cycle length, s
ventilation length, s
apnea length, s
circulatory delay, s
time to peak ventilation, s
BNP, ng/ml
HS Troponin T, pg/ml
PaO2, mmHg
PaCO2, mmHg
sO2, %
HCO3, mmol/l
ABE, mmol/l
pH
transcutaneously measured pCO2, mmHg
Cardiac output (CO)
Cardiac index (CI)
Stroke volume (SV)
Stroke volume index (SVI)
Stroke volume variation (SVV)
Systemic vascular resistence (SVR)
Systemic vascular resistence index (SVRI)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Trial after 20 patients have completed the study procedures. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |