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

This study is currently recruiting participants.
Verified July 2012 by Brigham and Women's Hospital
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Atul Malhotra, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01377987
First received: June 20, 2011
Last updated: October 19, 2012
Last verified: July 2012
History of Changes
  Purpose

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 least severe ventilatory control instability (lowest 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 Intervention
Heart Failure
 Drug: Acetazolamide
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Physiological Study to Predict Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • The severity of sleep disordered breathing (apnea-hypopnea index, AHI) [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Nocturnal arterial oxygenation, sleep efficiency, percent of stable breathing time will also be assessed.


Secondary Outcome Measures:
  • Ventilatory stability, i.e. loop gain, ventilatory sensitivity to carbon dioxide [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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.

  • Sympathetic activity (urinary norepinephrine) [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Plasma norepinephrine and epinephrine, and urinary epinephrine will be measured to confirm results.

  • Cardiac function, assessed by echocardiography [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Volumes, hemodynamics, and strain will be assessed.

  • Closing volume [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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.

  • Brain natriuretic peptide (BNP and NT-proBNP) [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Other known biomarkers will also be assessed in parallel to confirm any observed benefit

  • Subjective sleep quality, breathlessness, fatigue (Quality of life) [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Troponin I [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Other known biomarkers will also be assessed in parallel to confirm any observed benefit


Estimated Enrollment: 85
Study Start Date: August 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acetazolamide Drug: Acetazolamide
4 mg/kg, once daily before bed, for 8 days
Other Name: Diamox
Placebo Comparator: Sugar pill Drug: Placebo
4 mg/kg, once daily before bed, for 8 days

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • LVEF<50%
  • Age 18-80

Exclusion Criteria:

  • severe obstructive respiratory disease
  • unstable heart failure status
  • recent use of positive airway pressure therapy
  • current use of medications known to affect ventilation
  • severe kidney disease
  • hemoglobin <9.5g/dl (moderate-severe anemia)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01377987

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Scott A Sands, PhD         sasands@partners.org    
Sponsors and Collaborators
Atul Malhotra, MD
American Heart Association
Investigators
Principal Investigator: Atul Malhotra, MD Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Atul Malhotra, MD, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01377987     History of Changes
Other Study ID Numbers: 2011-P-000049/1
Study First Received: June 20, 2011
Last Updated: October 19, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Sleep Apnea Syndromes
Heart Diseases
Cardiovascular Diseases
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Acetazolamide
 Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 19, 2013