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

Phase 4

Completed

• Conditions: Heart Failure With Normal Ejection Fraction; Chronotropic Incompetence
• Interventions: Drug: Controlled withdrawal of beta-blockers; Diagnostic Test: Cardiopulmonary Exercise Testing

• Registration Number: NCT03871803
• Lead Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia

Brief Summary

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

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 Timeline

• Study Start: 2018-10-01
• Study First Submitted: 2019-03-03
• Study First Submitted QC: 2019-03-09
• Study First Posted: 2019-03-12
• Status Verified: 2020-07
• Primary Completion: 2021-02-27
• Study Completion: 2021-02-27
• Last Update Submitted: 2021-02-27
• Last Update Posted: 2021-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm A	Controlled withdrawal of beta-blockers	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
Arm A	Cardiopulmonary Exercise Testing	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
Arm B	Controlled withdrawal of beta-blockers	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.
Arm B	Cardiopulmonary Exercise Testing	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.

Primary Outcome Measures

Name	Time	Method
Maximal functional capacity	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 .

Secondary Outcome Measures

Name	Time	Method
Cognitive evaluation	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.
Quality of life evaluation	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
Security: reporting on potential clinical adverse outcomes	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

Trial Locations

Locations (1)

INCLIVA; 🇪🇸 Valencia, Spain