Beta Blocker IntoleranceRESTORENCT02173028
RESynchronizaTiOn theRapy and bEta-blocker Titration
An observational study of Beta Blocker Intolerance and Congestive Heart Failure, run by Giuseppe Ricciardi at 4 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Beta Blocker Intolerance, Congestive Heart Failure
- How many people
- 254 participants
- Where
- 4 sitesItaly
- Study dates
- Jun 2013to Jul 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Ospedale Monaldi SUN
Naples, 80131
Ospedale Monaldi
Naples, 80131
Policlinico Federico II
Naples
Policlinico Casilino
Rome, RM, 00100
About this study
Official title: 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.
Read the 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.
- Conditions
- Beta Blocker Intolerance, Congestive Heart Failure
- Keywords
- Beta Blocker Intolerance;, Remote Patient Management system;, Cardiac Resynchronization Therapy
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (2)
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.
Measured: 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study startJun 2013
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Beta Blocker IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 254 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giuseppe Ricciardi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Giuseppe Ricciardi, University of Florence
- Investigators
- Edoardo Gronda, Principal investigator, MultiMedica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02173028
- Sponsor's protocol ID
- Rif. n. 89/11 - 2011/0043537
- Acronym
- RESTORE
- Status last verified
- Feb 2017
- First submitted
- 23 Jun 2014
- Last updated
- 24 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 28188000
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RESynchronizaTiOn theRapy and bEta-blocker Titration : RESTORE
- ClinicalTrials.gov ID
- NCT02173028
- Acronym / sponsor ID
- RESTORE / Rif. n. 89/11 - 2011/0043537
- Conditions
- Beta Blocker Intolerance, Congestive Heart Failure
- Keywords
- Beta Blocker Intolerance;, Remote Patient Management system;, Cardiac Resynchronization Therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- Giuseppe RicciardiUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 24 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (6 listed)
- 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 ;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Optimal beta-blockers titration due to CRT
Time frame: 3 months
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.
2 secondary outcomes
Beta-blocker Titration with telemedicine system
Time frame: 3 months
Clinical response to CRT
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
- Derived from this study: PubMed 28188000D'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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edoardo Gronda principal investigator
MultiMedica
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Beta Blocker Intolerance and Congestive Heart Failure, run by Giuseppe Ricciardi at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal beta-blockers titration due to CRT (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02173028, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2017.