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Predicting Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients (HF-ACZ)

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ClinicalTrials.gov Identifier: NCT01377987
Recruitment Status : Completed
First Posted : June 22, 2011
Results First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Sponsor:
Collaborators:
American Heart Association
National Institutes of Health (NIH)
Information provided by (Responsible Party):
David Andrew Wellman, Brigham and Women's Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Heart Failures Drug: Acetazolamide Drug: Placebo Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Physiological Study to Predict Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients
Study Start Date : August 2011
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Acetazolamide Drug: Acetazolamide
4 mg/kg, once daily before bed, for 7 days
Other Name: Diamox

Placebo Comparator: Sugar pill Drug: Placebo
4 mg/kg, once daily before bed, for 7 days




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01377987


Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
David Andrew Wellman
American Heart Association
National Institutes of Health (NIH)
Investigators
Principal Investigator: Andrew Wellman, MD, PhD Brigham and Women's Hospital
Principal Investigator: Atul Malhotra, MD Brigham and Women's Hospital

Responsible Party: David Andrew Wellman, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01377987     History of Changes
Other Study ID Numbers: 2011-P-000049/1
First Posted: June 22, 2011    Key Record Dates
Results First Posted: June 13, 2018
Last Update Posted: June 13, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Acetazolamide
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs