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

NCT03871803 | Completed Phase 4 DMC

• 2 other identifiers: BBLOQ-20172017-005077-39
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

Conditions

Heart Failure With Normal Ejection Fraction; Chronotropic Incompetence

Keywords

Heart failure with preserved ejection fraction; Chronotropic incompetence; Functional capacity; Quality of life

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Cognitive evaluation

  The change in MMSE score will be measured at baseline, at 15-day and at 30-day

• Cognitive evaluation

  The change in MoCa score will be measured at baseline, at 15-day and at 30-day

• Quality of life evaluation

  The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day

• 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

Study Arms (2)

Arm A

ACTIVE COMPARATOR

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; Diagnostic Test: Cardiopulmonary Exercise Testing

Arm B

ACTIVE COMPARATOR

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; Diagnostic Test: Cardiopulmonary Exercise Testing

Interventions

Controlled withdrawal of beta-blockers DRUG

Controlled withdrawal of previos doses of beta-blockers after diagnosis of chronotropic incompetence

Arm A; Arm B

Cardiopulmonary Exercise Testing DIAGNOSTIC_TEST

Cardiopulmonary Exercise Testing to evaluate the chronotropic incompetence and the primary endpoint (functional capacity)

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (1)

INCLIVA

Valencia, 46010, Spain

Location

Related Publications (6)

• 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.

  PMID: 29573575 BACKGROUND

• 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.

  PMID: 29598943 BACKGROUND

• 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.

  PMID: 27206819 BACKGROUND

• Palau P, de la Espriella R, Seller J, Santas E, Dominguez E, Bodi V, Sanchis J, Nunez E, Bayes-Genis A, Bertomeu-Gonzalez V, Meyer M, Nunez J. beta-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. 2024 Apr 1;9(4):392-396. doi: 10.1001/jamacardio.2023.5500.

  PMID: 38324280 DERIVED

• 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.

  PMID: 34794685 DERIVED

• 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.

  PMID: 32073676 DERIVED

MeSH Terms

Interventions

Exercise Test

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Officials

• Julio Núñez, MD, PhD

  Instituto de Investigacion Sanitaria INCLIVA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The examination tests will be performed by two blinded cardiologist to patients' allocation group
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor

Model Details: 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.

Study Record Dates

• First Submitted: March 3, 2019
• First Posted: March 12, 2019
• Study Start: October 1, 2018
• Primary Completion: February 27, 2021
• Study Completion: February 27, 2021
• Last Updated: March 2, 2021

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)