β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity (Preserve-HR) - Clinical Trial for Heart Failure With Normal Ejection Fraction | NCT03871803

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Controlled withdrawal of beta-blockers

Cardiopulmonary Exercise Testing

About this trial

This is an interventional treatment trial for Heart Failure With Normal Ejection Fraction focused on measuring Heart failure with preserved ejection fraction, Chronotropic incompetence, Functional capacity, Quality of life

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

INCLIVA

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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 .

Secondary Outcome Measures

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.

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.

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

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

Full Information

NCT ID

NCT03871803

First Posted

March 3, 2019

Last Updated

February 27, 2021

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

1. Study Identification

Unique Protocol Identification Number

NCT03871803

Brief Title

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

Acronym

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

October 1, 2018 (Actual)

Primary Completion Date

February 27, 2021 (Actual)

Study Completion Date

February 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia

4. Oversight

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

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure With Normal Ejection Fraction, Chronotropic Incompetence

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

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.

Masking

Investigator

Masking Description

The examination tests will be performed by two blinded cardiologist to patients' allocation group

Allocation

Randomized

Enrollment

52 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

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 Title

Arm B

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Controlled withdrawal of beta-blockers

Intervention Description

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

Intervention Type

Diagnostic Test

Intervention Name(s)

Cardiopulmonary Exercise Testing

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximal functional capacity

Description

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 .

Time Frame

The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day

Secondary Outcome Measure Information:

Title

Cognitive evaluation

Description

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.

Time Frame

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

Title

Cognitive evaluation

Description

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.

Time Frame

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

Title

Quality of life evaluation

Description

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

Time Frame

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

Title

Security: reporting on potential clinical adverse outcomes

Description

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

Time Frame

Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Julio Núñez, MD, PhD

Organizational Affiliation

INCLIVA

Official's Role

Principal Investigator

Facility Information:

Facility Name

INCLIVA

City

Valencia

ZIP/Postal Code

46010

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

No

Citations:

PubMed Identifier

29573575

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.

Results Reference

background

PubMed Identifier

29598943

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.

Results Reference

background

PubMed Identifier

27206819

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. Erratum In: Eur Heart J. 2016 Dec 30;:

Results Reference

background

PubMed Identifier

34794685

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. Erratum In: J Am Coll Cardiol. 2022 Mar 1;79(8):848.

Results Reference

derived

PubMed Identifier

32073676

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.

Results Reference

derived

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

Heart Failure With Normal Ejection Fraction, Chronotropic Incompetence

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial