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

Heart Failure With Normal Ejection Fraction Clinical Trial

— Preserve-HR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03871803
• Other study ID #: BBLOQ-2017
• Secondary ID: 2017-005077-39
• Status: Completed
• Phase: Phase 4
• Start date: October 1, 2018
• Est. completion date: February 27, 2021

Study information

• Verified date: July 2020
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 27, 2021
• Est. primary completion date: February 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronotropic Incompetence
• Heart Failure
• Heart Failure With Normal Ejection Fraction

Intervention

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)

Locations

Country	Name	City	State
Spain	INCLIVA	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Domínguez E, Palau P, Núñez E, Ramón JM, López L, Melero J, Bellver A, Santas E, Chorro FJ, Núñez J. Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction. ESC Heart Fail. 2018 Aug;5(4):579-585. doi: 10.1002/ehf2.12281. Epub 2018 Mar 24. — View Citation

Palau P, Domínguez E, Sanchis J, Bayés-Genis A, Núñez J. Heart Rate in Heart Failure With Preserved Ejection Fraction: Another Example of the Heterogeneity of This Syndrome. JACC Heart Fail. 2018 Apr;6(4):350-351. doi: 10.1016/j.jchf.2017.12.003. — View Citation

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. Erratum in: Eur Heart J. 2016 Dec 30;:. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal functional capacity	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	Cognitive evaluation	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
Secondary	Cognitive evaluation	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
Secondary	Quality of life evaluation	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
Secondary	Security: reporting on potential clinical adverse outcomes	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