Sleep Apnea and CRT Upgrading

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01970423
Recruitment Status : Recruiting
First Posted : October 28, 2013
Last Update Posted : March 21, 2018
Information provided by (Responsible Party):
Wolfgang Dichtl, MD PhD, Medical University Innsbruck

Brief Summary:
Cardiac resynchronization therapy may reduce central sleep apnea, but there is no prospective randomized study so far demonstrating such an effect in patients with conventional pacemaker undergoing upgrading to CRT because of heart failure.

Condition or disease Intervention/treatment Phase
Cardiomyopathy Device: CRT Device: conventional right ventricular stimulation Not Applicable

Detailed Description:

Within the last decade cardiac resynchronization therapy (CRT) has been proven to be an effective therapy to reduce morbidity and mortality in chronic heart failure patients with wide QRS complex, in particular complete left bundle branch block. New indications have recently been established, including patients with mild symptoms and patients in need of conventional pacing such as high-grade atrioventricular block.

More than half - up to 80% - of patients with heart failure suffer from concomitant sleep apnea (SA), which further worsens symptoms and prognosis. Cardiac resynchronization therapy may ameliorate sleep apnea, but only the central form of sleep apnea (CSA). However, only very small uncontrolled studies with mainly less than 20 patients have been reported so far concerning the interactions between CRT and sleep apnea, and no data are available in patients with conventional right ventricular pacing undergoing upgrading to CRT.

Therefore, we want to perform a study called UPGRADE which is characterized

  • being the first randomized study comparing the effects of new-onset cardiac resynchronization therapy on moderate and severe central sleep apnea, defined by an AHI ≥ 15/h as assessed by polysomnography in patients with conventional right ventricular pacing which is known to decrease cardiac function, induce heart failure and atrial fibrillation
  • using a new technology called AP Scan® which enables continuous and reliable monitoring of sleep-disordered breathing (SDB); this technology is further validated with polysomnography, the gold standard in the diagnosis and follow-up in patients with sleep apnea

Unfortunately, one third of patients still do not benefit from CRT (so-called non-responders). On the other hand, up to 20% of patients greatly benefit and completely recover in terms of normalization of left ventricular ejection fraction and/or functional capacity (so-called super-responders). Research is urgently needed to decrease the number of non-responders and increase the number of super-responders.

Patient selection is still based on QRS duration and its morphology. Echocardiography and other imaging techniques for mechanical dyssynchrony assessment have failed to be a useful predictor for adequate patient selection. Therefore, we further want to test whether CRT itself does not only improve concomitant sleep apnea, but also if preexisting sleep apnea predicts the response to CRT in patients with previously conventional right-ventricular pacing undergoing an upgrade to CRT by additional implantation of a left ventricular lead.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Central Sleep Apnea and New-onset Cardiac Resynchronization in Patients With Conventional Pacemaker or ICD Therapy: a Multicenter, Randomized Clinical Trial
Study Start Date : January 2014
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea
U.S. FDA Resources

Arm Intervention/treatment
After randomization and polysomnography the CRT will get activated. After 3-5 months cross over to conventional right ventricular stimulation.
Device: CRT
The new device is the first CRT-P that relies on a physiological parameter, respiration, to allow the pacemaker to follow the patient's breath and help create an appropriate pacing rate.
Other Names:
  • INLIVEN (Boston Scientific)
  • INCEPTA (Boston Scientific)
Right Ventricular Stimulation
After randomization and polysomnography the conventional right ventricular stimulation will get activated. After 3-5 months cross over to CRT activation.
Device: conventional right ventricular stimulation

Primary Outcome Measures :
  1. Improvement of central sleep apnea [ Time Frame: January 2014 - December 2016 ]

    improvement of moderate / severe central sleep apnea (AHI ≥ 15/h) due to new onset CRT as compared to ongoing conventional right ventricular pacing

    • reduction of mean RDI (respiratory disturbance index) as assessed by AP Scan® in the first 90-150 days after initiation to CRT as compared to conventional RV pacing
    • reduction of AHI (apnea-hypopnea index) as assessed by polysomnography within 90-150 days after initiation to CRT as compared to conventional RV pacing

  2. Validation of the AP scan by the gold standard polysomnography [ Time Frame: January 2014 - December 2016 ]

Secondary Outcome Measures :
  1. CRT response [ Time Frame: January 2014 - December 2016 ]

    secondary endpoints = CRT response according to pre-existing sleep apnea (RDI 0-14/h versus ≥ 15/h)

    • improvement of left ventricular ejection fraction and reduction in left ventricular endsystolic volume as assessed by transthoracic echocardiography
    • decrease in NTproBNP / BNP plasma concentration

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • left ventricular ejection fraction < 50%
  • implanted conventional pacemaker or ICD with a right ventricular pacing rate > 40% or planned "ablate and pace" therapy
  • age 40 - 85 years

Exclusion Criteria:

  • liver cirrhosis
  • renal insufficiency (GFR < 30ml/min/1,73m²)
  • expectancy of life < 1 year
  • premenopausal woman
  • drug or substance abuse
  • hyperthyreosis
  • custodianship
  • CM allergy
  • any condition that may compromise the compliance of the patient, or would preclude the patient from successful completion of the study
  • plaster allergy
  • enrollment in another clinical trial

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 identifier (NCT number): NCT01970423

Contact: Wolfgang Dicht, MD +43-512-504-81388

Medical University Innsbruck, Department for Internal Medicine III Not yet recruiting
Innsbruck, Austria, 6020
Contact: Wolgang Dichtl, PD Dr.    +43-512-504-81388   
Principal Investigator: Wolfgang Dichtl, MD         
Medical University Innsbruck, Internal Medicine III (Cardiology & Angiology) Recruiting
Innsbruck, Austria, 6020
Contact: Wolfgang Dichtl, MD, PhD    004351250481388   
Contact: Florian Hintringer, MD    004351250481312   
Sponsors and Collaborators
Medical University Innsbruck
Principal Investigator: Wolfgang Dichtl, MD Medical University of Innsbruck

Responsible Party: Wolfgang Dichtl, MD PhD, Priv.-Doz. DDr., Medical University Innsbruck Identifier: NCT01970423     History of Changes
Other Study ID Numbers: UPGRADE
First Posted: October 28, 2013    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018

Keywords provided by Wolfgang Dichtl, MD PhD, Medical University Innsbruck:
Patients with pacemaker or ICD therapy

Additional relevant MeSH terms:
Heart Diseases
Cardiovascular Diseases