Clinical trial NCT02173028: RESynchronizaTiOn theRapy and bEta-blocker Titration
Official title: RESynchronizaTiOn theRapy and bEta-blocker Titration : RESTORE
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Beta Blocker Intolerance
Congestive Heart Failure
Keywords: Beta Blocker Intolerance;
Remote Patient Management system;
Cardiac Resynchronization Therapy
Lead sponsor: University of Florence
Sponsor class: OTHER
First posted: 2014-06-24
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients successfully implanted with CRT-D according to current European guidelines, on optimal therapy for heart failure (diuretics, ACE inhibitors and aldosterone antagonists), with stable dose in the previous month.

Brief summary: Patients will be treated according to the clinical practice of the participating centers and to the international guidelines for the treatment of heart failure.The present analysis provides a collection of data about the changes to drug therapy after the "Cardiac Resynchronization Therapy" (CRT) procedure , and any signs and symptoms of intolerance to prescribed medications.

Detailed description: The treatment of chronic heart failure is currently based on the use of ACE (Angiotensin Converting Enzyme) inhibitors and beta-blockers. Although this therapy is universally accepted up to 10-20% of patients may be intolerant. Moreover, the majority of patients are not treated with the doses that have been shown to be effective in controlled clinical trials. Although it is possible that even low doses of neurohumoral inhibitors are still effective than placebo, a greater benefit can be obtained at maximum doses. Therefore, it is generally recommended that these agents are used at recommended doses found to be effective in controlled studies. There are many reasons for the lack of prescription neurohumoral inhibitors and their use in non-optimal doses. These include both an inadequate clinical management, and low tolerance to drugs. As far as beta-blockers, their poor tolerability has at least two main causes: 1) the effects not related to heart failure (eg, bradycardia, AtrioVentricular (AV) block, bronchial asthma), 2) the acute negative inotropic effects, which can cause a further deterioration of hemodynamic parameters.

The primary objective of the analysis is to demonstrate that cardiac resynchronization therapy (CRT) may allow titration of beta-blockers (carvedilol or bisoprolol) until the optimal dosage, or at least to the effective dose, in patients with heart failure treated to maximal doses of beta-blockers and with the indications for CRT according to current international guidelines.

The secondary objective is to evaluate the effectiveness of remote monitoring with a telemedicine system to facilitate the automatic titration of beta-blockers in comparison with the standard approach, which consists of periodic outpatient visits. The strategy adopted will depend on the availability of remote monitoring systems and standard clinical practice of each participating center.

In addition, we will evaluate the clinical response to CRT, depending on the optimal or sub-optimal dosage of beta-blockers.

Eligibility criteria: Inclusion Criteria:

* Patients on optimal therapy for heart failure (diuretics, ACE inhibitors and aldosterone antagonists), with stable dose in the previous month;
* Successfully implanted with CRT-D according to current European Society of Cardiology (ESC) guidelines;
* New York Heart Association (NYHA) functional class: II, III and IV;
* Left Ventricular Ejection Fraction (LVEF) ≤ 35%;
* Duration of ventricular depolarization wave (QRS) ≥ 120ms (NYHA III or IV) or ≥ 150ms in NYHA II;
* Patients with chronic atrial fibrillation will be eligible for the study only if they undergo ablation ;
* 18 years or above

Exclusion Criteria:

* Failure to comply with the scheduled follow-up;
* Life expectancy less than 12 months ;
* Pregnant women;
* Tricuspid valve mechanics;
* Severe aortic stenosis or other valve disease ;
* Patients already receiving CRT.

Primary outcomes:
measure: Optimal beta-blockers titration due to CRT
timeFrame: 3 months
Secondary outcomes:
measure: Beta-blocker Titration with telemedicine system
timeFrame: 3 months
measure: Clinical response to CRT
timeFrame: 12 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Policlinico Casilino
state: RM
city: Napoli
country: Italy
facility: Ospedale Monaldi SUN
city: Napoli
country: Italy
facility: Ospedale Monaldi
city: Napoli
country: Italy
facility: Policlinico Federico II
Study officials:
affiliation: MultiMedica
name: Edoardo Gronda
role: PRINCIPAL_INVESTIGATOR
References:
citation: D'Onofrio A, Palmisano P, Rapacciuolo A, Ammendola E, Calo L, Ruocco A, Bianchi V, Maresca F, Del Giorno G, Martino A, Mauro C, Campari M, Valsecchi S, Accogli M. Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study. Int J Cardiol. 2017 Jun 1;236:290-295. doi: 10.1016/j.ijcard.2017.02.015. Epub 2017 Feb 5.