β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity (Preserve-HR) (Preserve-HR)

February 27, 2021 updated by: Julio Nuñez, Fundación para la Investigación del Hospital Clínico de Valencia

Betablockers Withdrawal in Patients With Heart Failure With Preserved Ejection Fraction and Chronotropic Incompetence: Effect on Functional Capacity Rationale and Study Design of a Prospective, Randomized, Controlled Trial

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence has emerged as a crucial mechanism, particularly in elderly patients. Betablockers, drugs with negative chronotropic effect, are commonly used in HFpEF, despite current evidence does not support its routine use in these patients. The aim of this work is to evaluate the effect of betablockers withdrawal in patients with HFpEF and chronotropic incompetence on functional capacity assessed by the peak oxygen consumption at maximal exercise (peakVO2) at 15 and 30 days after the intervention

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, crossover, randomized (1:1) and single center study. After randomization, clinical and cardiac rhythm will be continuously registered during 30 days. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 15 and 30-day in both groups. Patients with HFpEF, functional class NYHA II-III, chronic treatment with betablockers, and chronotropic incompetence will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 15% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD±2.5)] of 52 patients would be necessary to test our hypothesis.

In conclusion, optimizing therapy that improve quality of life and autonomy has become a health care priority in HFpEF. The investigators believe this study will add important knowledge for the treatment of a subgroup of HFpEF.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valencia, Spain, 46010
        • INCLIVA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Stable symptomatic patients with heart failure and preserved ejection fraction (NYHA class II-III).
  • NT-proBNP >125 pg/mL in the last month
  • Previous treatment with beta-blockers during the last 3 months
  • Documented chronotropic incompetence, defined as: [(heart rate at peak exercise- heart rate at baseline)] / [(220 - age) - (heart rate at baseline)] < 0.62

Exclusion Criteria:

  • Moderate to severe valvulopathy or miocardiopathy associated
  • Patient with heart failure with recovered ejection fraction
  • Acute Coronary Syndrome in the previous 12 months
  • Angina or signs of myocardial ischemia on cardiopulmonary exercise testing
  • Baseline heart rate>75 bpm.
  • Uncontrolled hypertension, defined as >140mmHg systolic blood pressure and/or >90 mmHg diastolic blood pressure.
  • Moderate to severe pulmonary disease associated
  • Extracardiac comorbidity with a life expentancy less than 1 year.
  • Unable to perform an adequate cardiopulmonary exersice test
  • Previous treatment with digitalis or calcium channel blockers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A

Controlled Withdrawal of Beta-blockers and Cardiopulmonary Exercise Testing (CPET) Patient will be assessed for chronotr0pic incompetence by CPET. If the patient exhibits chronotropic incompetence, we will reduce half dose of previous beta-blocker.

A cardiologist will evaluate clinically the the patient and the heart rate in 3 days. If clinical and heart rate stability (below 90 bpm), the patients will withdraw the beta-blocker and will be assessed by CPET at 15-day.

After second CPET, the patient will introduce the half-dose of beta-blocker and will be evaluated in 3 days. If clinical stability, the patient will introduce the previous dose of beta-blocker A third CPET will be performed at 15-day
Drug: Controlled withdrawal of beta-blockers
Controlled withdrawal of previos doses of beta-blockers after diagnosis of chronotropic incompetence
Diagnostic test: Cardiopulmonary Exercise Testing
Cardiopulmonary Exercise Testing to evaluate the chronotropic incompetence and the primary endpoint (functional capacity)
Active Comparator: Arm B

Cardiopulmonary Exercise Testing (CPET) and Controlled Withdrawal of Beta-blockers Patient will be assessed for chronotropic incompetence by CPET.If the patient exhibits chronotropic incompetence, a cardiologist will evaluate clinically the patient and the heart rate in 3 days and will be assessed by CPET at 15-day.

After second CPET, the patient will reduce half dose of previous beta-blocker. A cardiologist will evaluate clinically the the patient and the heart rate in 3 days. If clinical and heart rate stability (below 90 bpm), the patients will withdraw the beta-blocker and will be assessed by CPET at 15-day.
Drug: Controlled withdrawal of beta-blockers
Controlled withdrawal of previos doses of beta-blockers after diagnosis of chronotropic incompetence
Diagnostic test: Cardiopulmonary Exercise Testing
Cardiopulmonary Exercise Testing to evaluate the chronotropic incompetence and the primary endpoint (functional capacity)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal functional capacity
Time Frame: The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day
Maximal functional capacity measured by peak oxygen consumption in the cardiopulmonary exercise testing (CPET). The peak oxygen consumption is expressed in mL/kg/min.The investigators will measure the change of peak oxygen consumption .
The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive evaluation
Time Frame: The change in MMSE score will be measured at baseline, at 15-day and at 30-day
We will asses the cognitive function by Mini Mental State Examination (MMSE) The MMSE is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score.
The change in MMSE score will be measured at baseline, at 15-day and at 30-day
Cognitive evaluation
Time Frame: The change in MoCa score will be measured at baseline, at 15-day and at 30-day
We will asses the cognitive function by Montreal Cognitive Assessment (MoCa) The MoCa is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score.
The change in MoCa score will be measured at baseline, at 15-day and at 30-day
Quality of life evaluation
Time Frame: The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day
We will asses the quality of life by Minnesota living with heart failure questionnaire (MLHFQ). The MLHFQ is a quality of life questionnarie .The investigators will asses the changes in the full questionnarie. We will report the total score. The score is ranged from 0-105. 105 points is the worse outcome
The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day
Security: reporting on potential clinical adverse outcomes
Time Frame: Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day
Evaluation of adverse clinical outcomes during the study. The investigators will evaluate the composite of the following adverse events: mortality and/or readmissions due to cardiovascular reasons. The investigators will assess differences between both groups/arms
Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

Investigators

  • Principal Investigator: Julio Núñez, MD, PhD, INCLIVA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2018

Primary Completion (Actual)

February 27, 2021

Study Completion (Actual)

February 27, 2021

Study Registration Dates

First Submitted

March 3, 2019

First Submitted That Met QC Criteria

March 9, 2019

First Posted (Actual)

March 12, 2019

Study Record Updates

Last Update Posted (Actual)

March 2, 2021

Last Update Submitted That Met QC Criteria

February 27, 2021

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBLOQ-2017
  • 2017-005077-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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