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Completed

NCT Number: NCT01377987

Predicting Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients

The ultimate goal is to improve our understanding of the pathophysiology and resistance to effective treatment of sleep disordered breathing in patients with heart failure, with a focus on selecting patients that will benefit specifically from acetazolamide treatment.

The study addresses three primary hypotheses: 1) Acetazolamide treatment will reduce the apnea-hypopnea index and improve markers of heart-failure severity in heart-failure patients with sleep apnea. 2) Acetazolamide will provide the greatest improvement in patients with the most severe ventilatory control instability (strongest chemoreflex response to carbon dioxide; highest loop gain). 3) Acetazolamide will act primarily via stabilizing ventilatory control (reducing loop gain), rather than via improvement to upper airway anatomy, pulmonary congestion, and cardiac function.

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Key information

Age range

18 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(Heart failure patients)

  • Left ventricular ejection fraction (EF) <50%, or heart failure with preserved EF
  • Age 18-89

Exclusion criteria

  • severe obstructive respiratory disease
  • unstable heart failure status
  • recent use of positive airway pressure therapy
  • current use of opioids, benzodiazepines
  • severe kidney disease
  • severe anemia

Treatment and study plan

Acetazolamide

Drug

4 mg/kg, once daily before bed, for 7 days

Other names: Diamox

Placebo

Drug

4 mg/kg, once daily before bed, for 7 days

Primary outcomes

  1. The Severity of Sleep Disordered Breathing (Apnea-hypopnea Index, AHI)

    Time frame: 1 week

    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.

Secondary outcomes

  1. Ventilatory Chemoreflex Sensitivity, "Loop Gain" Using Carbon Dioxide Pulses

    Time frame: 1 week

    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.

  2. Sympathetic Activity (Urinary Norepinephrine)

    Time frame: 1 week

    Urinary norepinephrine levels overnight

  3. Left-atrial Volume

    Time frame: 1 week

    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).

  4. Brain Natriuretic Peptide (NT-proBNP)

    Time frame: 1 week

    Brain natriuretic peptide (NT-proBNP) in morning

  5. Pittsburgh Sleep Quality Index

    Time frame: 1 week

    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.

Sponsors and collaborators

Lead sponsor

David Andrew Wellman

Other

Collaborators

  • American Heart Association
  • National Institutes of Health (NIH)

Registry information

Official study title

Physiological Study to Predict Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients

Acronym: HF-ACZ

Important dates

Study start
2011
Primary completion
2016
Study completion
2016
First posted
Jun 22, 2011
Registry last updated
Jun 13, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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