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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
Last Update Posted : January 6, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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
Heart Failures Controls Without Heart Failure Drug: Acetazolamide Drug: Placebo

Study Design

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
Primary Completion Date : December 2016
Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

Primary Outcome Measures :
  1. The severity of sleep disordered breathing (apnea-hypopnea index, AHI) [ Time Frame: 1 week ]
    Nocturnal arterial oxygenation and percent of stable breathing time will also be assessed.


Secondary Outcome Measures :
  1. Ventilatory stability, i.e. loop gain, ventilatory sensitivity to carbon dioxide [ Time Frame: 1 week ]
    The severity of ventilatory instability is expected to predict treatment failure, and the magnitude of its improvement is expected to be associated with a positive primary outcome.

  2. Sympathetic activity (urinary norepinephrine) [ Time Frame: 1 week ]
    Plasma norepinephrine and epinephrine will be measured to confirm results.

  3. Cardiac function, assessed by echocardiography [ Time Frame: 1 week ]
    Volumes and hemodynamics will be assessed.

  4. Closing volume [ Time Frame: 1 week ]
    Higher pulmonary closing volume can indicate subclinical pulmonary edema, which is expected to improve if there is any considerable diuretic effect of acetazolamide or reduction in left ventricular filling pressure. Respiratory system conductance will also be assessed.

  5. Brain natriuretic peptide (NT-proBNP) [ Time Frame: 1 week ]
    Other known biomarkers will also be assessed in parallel to confirm any observed benefit

  6. Subjective sleep quality, breathlessness, fatigue (Quality of life) [ Time Frame: 1 week ]
    pittsburgh sleep quality index; kansas city cardiomyopathy questionnaire

  7. Troponin I [ Time Frame: 1 week ]
    Other known biomarkers will also be assessed in parallel to confirm any observed benefit


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Senior)
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

Inclusion Criteria (Controls)

  • No history or evidence of heart failure
  • 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
Contacts and Locations

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
More Information

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
Last Update Posted: January 6, 2017
Last Verified: January 2017

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