RESynchronizaTiOn theRapy and bEta-blocker Titration (RESTORE)

RESynchronizaTiOn theRapy and bEta-blocker Titration : RESTORE

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.

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure; Beta Blocker Intolerance

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.

• Study Type: Observational
• Enrollment (Actual): 254

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy
    • Policlinico Federico II
  • Napoli, Italy, 80131
    • Ospedale Monaldi
  • Napoli, Italy, 80131
    • Ospedale Monaldi SUN
  • RM
    • Rome, RM, Italy, 00100
      • Policlinico Casilino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Optimal beta blocker titration; We will compare the efficacy of two management strategies for beta-blocker up-titration: Standard in-office visits vs. Remote follow-up.
Without optimal titration of beta blocker; This analysis will be conducted within the Cardiac Resynchronization Therapy observational study Modular Registry (CRT MORE - ClinicalTrials.gov Identifier: NCT01573091).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal beta-blockers titration due to CRT	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 goal is to achieve the optimal dosage of 10mg/die of bisoprolol or 50mg/die of carvedilol, or at least the recommended dose (carvedilol 37.5 mg / day or bisoprolol 7.5 mg), as shown in international treatment guidelines.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-blocker Titration with telemedicine system	The secondary objective is to evaluate the effectiveness of a Remote Patient Management (RPM) system to optimize the titration of beta-blockers in comparison with the standard approach, which consists of periodic in -hospital visits.	3 months
Clinical response to CRT	The response will be measured at 3 and 12 months in terms of: Amount of reverse remodeling of the left ventricle;; Changes in NYHA (New York Heart Association) functional class;; Ventricular arrhythmias treated by the Implantable Cardioverter Defibrillator (ICD);; Adverse cardiovascular events (cardiovascular hospitalization, heart failure hospitalization) and mortality from all causes.	12 months

Collaborators and Investigators

• Sponsor: Giuseppe Ricciardi
• Investigators: Principal Investigator: Edoardo Gronda, Multimedica

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: June 23, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Actual): February 24, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Cardiac Resynchronization Therapy; Beta Blocker Intolerance;; Remote Patient Management system
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Rif. n. 89/11 - 2011/0043537

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO