Clinical trial NCT03871803: β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure With Normal Ejection Fraction
Chronotropic Incompetence
Keywords: Heart failure with preserved ejection fraction
Chronotropic incompetence
Functional capacity
Quality of life
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
First posted: 2019-03-12
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model 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 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximal functional capacity
timeFrame: The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day
Secondary outcomes:
measure: Cognitive evaluation
timeFrame: The change in MMSE score will be measured at baseline, at 15-day and at 30-day
measure: Cognitive evaluation
timeFrame: The change in MoCa score will be measured at baseline, at 15-day and at 30-day
measure: Quality of life evaluation
timeFrame: The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day
measure: Security: reporting on potential clinical adverse outcomes
timeFrame: Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: INCLIVA
Study officials:
affiliation: INCLIVA
name: Julio Núñez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dominguez E, Palau P, Nunez E, Ramon JM, Lopez L, Melero J, Bellver A, Santas E, Chorro FJ, Nunez 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.
citation: Palau P, Dominguez E, Sanchis J, Bayes-Genis A, Nunez 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. No abstract available.
citation: Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-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. No abstract available.
citation: Palau P, Seller J, Dominguez E, Sastre C, Ramon JM, de La Espriella R, Santas E, Minana G, Bodi V, Sanchis J, Valle A, Chorro FJ, Llacer P, Bayes-Genis A, Nunez J. Effect of beta-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction. J Am Coll Cardiol. 2021 Nov 23;78(21):2042-2056. doi: 10.1016/j.jacc.2021.08.073.
citation: Palau P, Seller J, Dominguez E, Gomez I, Ramon JM, Sastre C, de la Espriella R, Santas E, Minana G, Chorro FJ, Gonzalez-Juanatey JR, Nunez J. Beta-blockers 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 Preserve-HR trial). Clin Cardiol. 2020 May;43(5):423-429. doi: 10.1002/clc.23345. Epub 2020 Feb 19.