Trial Outcomes & Findings for Predicting Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients (NCT NCT01377987)

Results Overview

The frequency of apneas and hypopneas (apnea-hypopnea index) was assessed. The primary measure was the value for non-REM supine sleep. A higher value indicates more severe sleep apnea. A value above 15 indicates the presence of moderate-to-severe sleep apnea.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

29 participants

Primary outcome timeframe

1 week

Results posted on

2018-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Acetazolamide First, Then Placebo Acetazolamide: 4 mg/kg, once daily before bed, for 7 days 1 week washout Placebo: 4 mg/kg, once daily before bed, for 7 days	Placebo First, Then Acetazolamide Placebo: 4 mg/kg, once daily before bed, for 7 days 1 week washout Acetazolamide: 4 mg/kg, once daily before bed, for 7 days
First Intervention (7 Days) STARTED	14	15
First Intervention (7 Days) COMPLETED	14	15
First Intervention (7 Days) NOT COMPLETED	0	0
Washout (7 Days) STARTED	14	15
Washout (7 Days) COMPLETED	13	14
Washout (7 Days) NOT COMPLETED	1	1
Second Intervention (7 Days) STARTED	13	14
Second Intervention (7 Days) COMPLETED	13	14
Second Intervention (7 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Acetazolamide First, Then Placebo Acetazolamide: 4 mg/kg, once daily before bed, for 7 days 1 week washout Placebo: 4 mg/kg, once daily before bed, for 7 days	Placebo First, Then Acetazolamide Placebo: 4 mg/kg, once daily before bed, for 7 days 1 week washout Acetazolamide: 4 mg/kg, once daily before bed, for 7 days
Washout (7 Days) Withdrawal by Subject	1	1

Baseline Characteristics

Predicting Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Patients n=29 Participants All patients randomized
Age, Continuous	60 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 week

Population: All participants who were randomized and completed the relevant study arm. Data are for non-REM supine sleep.

The frequency of apneas and hypopneas (apnea-hypopnea index) was assessed. The primary measure was the value for non-REM supine sleep. A higher value indicates more severe sleep apnea. A value above 15 indicates the presence of moderate-to-severe sleep apnea.

Outcome measures

Outcome measures
Measure	Acetazolamide n=28 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
The Severity of Sleep Disordered Breathing (Apnea-hypopnea Index, AHI) All participants	26.3 events per hour Standard Deviation 22.7	36.1 events per hour Standard Deviation 27.8
The Severity of Sleep Disordered Breathing (Apnea-hypopnea Index, AHI) Patients with sleep apnea	32.3 events per hour Standard Deviation 22.1	44.6 events per hour Standard Deviation 25.3

SECONDARY outcome

Timeframe: 1 week

Population: All participants who completed the relevant arm. Morning data are reported.

Chemoreflex "loop gain" was assessed according to Sands SA et al AJRCCM 2017 Jan 15;195(2):237-246. Loop gain is a unitless ratio measure that describes the magnitude of the increase in ventilation that occurs in response to a prior reduction in ventilation ("disturbance") and has units of L/min per L/min. A larger value indicates a more sensitive and unstable control system predisposing to oscillatory breathing. Loop gain was measured on the time scale of 1 min (i.e. response to a 1 cycle/min sinusoidal disturbance, referred to as "LG1"). The procedure involved brief administration of 7% carbon dioxide in air for 0.5 min ("pulses"); tests were repeated every 3 min for 30 min while measuring ventilation and carbon dioxide levels at the nose with patients awake and supine. measured using 0.5 min pulses of carbon dioxide.

Outcome measures

Outcome measures
Measure	Acetazolamide n=28 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
Ventilatory Chemoreflex Sensitivity, "Loop Gain" Using Carbon Dioxide Pulses	0.40 unitless Standard Deviation 0.16	0.49 unitless Standard Deviation 0.14

SECONDARY outcome

Timeframe: 1 week

Population: All participants who completed the relevant study arm

Urinary norepinephrine levels overnight

Outcome measures

Outcome measures
Measure	Acetazolamide n=28 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
Sympathetic Activity (Urinary Norepinephrine)	40.8 ug/g-creatinine Standard Deviation 23.6	35.0 ug/g-creatinine Standard Deviation 17.3

SECONDARY outcome

Timeframe: 1 week

Population: echocardiography could not be performed on one study due to rescheduling issues

Left-atrial volume index, echocardiography, bi-plane method. Lower values were considered a favorable outcome. We considered values ≤28 mL/m\^2 to indicate normal left atrial volume. Values indicating graded left atrial enlargement were described as follows: mild (29-33 mL/m\^2), moderate (34-39 mL/m\^2), severe (≥40 mL/m\^2).

Outcome measures

Outcome measures
Measure	Acetazolamide n=27 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
Left-atrial Volume	34.3 mL/m^2 Standard Deviation 12.1	40.0 mL/m^2 Standard Deviation 13.5

SECONDARY outcome

Timeframe: 1 week

Population: All participants who completed the relevant arm

Brain natriuretic peptide (NT-proBNP) in morning

Outcome measures

Outcome measures
Measure	Acetazolamide n=28 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
Brain Natriuretic Peptide (NT-proBNP)	919 pg/ml Standard Deviation 1320	932 pg/ml Standard Deviation 1403

SECONDARY outcome

Timeframe: 1 week

Population: All participants who participated in the relevant study arm.

Pittsburgh Sleep Quality Index is a measure of self-reported sleep quality containing 19 questions that make up 7 component scores that are added to provide a total score. Total scores range from 0-21 (units on a scale) with higher scores representing reduced sleep quality. A score of 5 or more is interpreted as reduced sleep quality. The total score is reported.

Outcome measures

Outcome measures
Measure	Acetazolamide n=28 Participants Acetazolamide (active arm)	Placebo n=28 Participants Placebo arm
Pittsburgh Sleep Quality Index	6.7 units on a scale Standard Deviation 3.6	7.5 units on a scale Standard Deviation 3.8

Adverse Events

Acetazolamide

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Acetazolamide n=28 participants at risk Acetazolamide (active arm)	Placebo n=28 participants at risk Placebo arm
General disorders Fall without injury	3.6% 1/28 • Number of events 1	0.00% 0/28
Renal and urinary disorders Nocturia	42.9% 12/28 • Number of events 12	3.6% 1/28 • Number of events 1
Metabolism and nutrition disorders Taste Disturbance	14.3% 4/28 • Number of events 4	0.00% 0/28
Nervous system disorders Paresthesias	17.9% 5/28 • Number of events 5	0.00% 0/28
General disorders Fatigue	10.7% 3/28 • Number of events 3	3.6% 1/28 • Number of events 1
Vascular disorders Lightheadedness upon standing	3.6% 1/28 • Number of events 1	3.6% 1/28 • Number of events 1
General disorders Headache	0.00% 0/28	3.6% 1/28 • Number of events 1
Gastrointestinal disorders Gastrointestinal discomfort	7.1% 2/28 • Number of events 2	7.1% 2/28 • Number of events 2
Eye disorders Dry eyes	3.6% 1/28 • Number of events 1	0.00% 0/28
General disorders Reduced exercise tolerance	0.00% 0/28	3.6% 1/28 • Number of events 1

Additional Information

Dr. Scott Sands

Brigham and Women's Hospital

Phone: 617 278 0911

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place