Clinical trial NCT01970423: Sleep Apnea and CRT Upgrading
Official title: Central Sleep Apnea and New-onset Cardiac Resynchronization in Patients With Conventional Pacemaker or ICD Therapy: a Multicenter, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiomyopathy
Keywords: Patients with pacemaker or ICD therapy
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2013-10-28
Enrollment: 56
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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:

* NYAH IV
* 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

Primary outcomes:
measure: Improvement of central sleep apnea
timeFrame: January 2014 - June 2021
measure: Validation of the AP scan by the gold standard polysomnography
timeFrame: January 2014 - June 2021
Secondary outcomes:
measure: CRT response
timeFrame: January 2014 - June 2021
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department for Internal Medicine III
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Internal Medicine III (Cardiology & Angiology)
Study officials:
affiliation: Medical University of Innsbruck
name: Wolfgang Dichtl, MD
role: PRINCIPAL_INVESTIGATOR
References: