search
Back to results

Training in HFpEF-PH (TRAIN HFpEF)

Primary Purpose

Pulmonary Hypertension Due to Left Heart Disease, Heart Failure With Preserved Ejection Fraction

Status
Not yet recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Exercise rehabilitation
Standard treatment
Sponsored by
Heidelberg University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension Due to Left Heart Disease

Eligibility Criteria

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

Inclusion Criteria:

  1. Female and male patients ≥18 years
  2. WHO/NYHA functional class II - IV
  3. PH with HFpEF diagnosed by right heart catheterisation showing:

    mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest; pulmonary arterial wedge pressure (PAWP) ≥15mmHg at rest or LVEDP ≥16mmHg and/or PAWP≥25 mmHg during exercise, and

  4. Preserved left ventricular ejection fraction ≥50%
  5. Patients receiving optimized therapy including intensified treatment with diuretics and who have been stable for 1 month before entering the study.
  6. Except for diuretics, medical treatment should not be changed during the study period.
  7. Able to understand and willing to sign the Informed Consent Form

Exclusion Criteria:

  1. Pre-capillary pulmonary hypertension (Group I; Group III; Group IV; Group V according to PH guidelines)
  2. Congenital or acquired severe valvular diseases (severe aortic stenosis or insufficiency, severe mitral valve stenosis or insufficiency)
  3. Pregnancy or lactation
  4. Walking disability
  5. Subject who participates in an interventional study during the course of this study
  6. Severe lung disease: FEV1/FVC <0.5 and total lung capacity <60% of the normal value
  7. Active myocarditis, unstable angina pectoris, exercise induced ventricular arrhythmias, active liver disease, porphyria or elevations of serum transaminases >3 x ULN (upper limit of normal) or bilirubin >1.5 x ULN
  8. Haemoglobin concentration less than 75% of the lower limit of normal
  9. Systolic blood pressure <85 mmHg
  10. History or suspicion of inability to cooperate adequately.

Sites / Locations

  • Centre for Pulmonary Hypertension at the Thoraxklinik Heidelberg, Heidelberg University Hospital
  • Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Exercise training

Standard treatment (waiting group)

Arm Description

Outcomes

Primary Outcome Measures

6-minute walking distance

Secondary Outcome Measures

WHO functional class
Quality of life physical component scale SF-36
Quality of life mental component scale SF-36
peak oxygen consumption
peak oxygen consumption/kg body weight
workload achieved during cardiopulmonary exercise testing
NT-proBNP (N-terminal pro brain natriuretic peptide)
Tricuspid annular plane systolic excursion
echocardiography
Systolic pulmonary arterial pressure
echocardiography
Right atrial area
echocardiography
Right ventricular area
echocardiography
Right ventricular pump function
echocardiography
Left ventricular pump function
echocardiography
Left ventricular eccentricity index
echocardiography

Full Information

First Posted
July 14, 2022
Last Updated
September 14, 2022
Sponsor
Heidelberg University
search

1. Study Identification

Unique Protocol Identification Number
NCT05464238
Brief Title
Training in HFpEF-PH
Acronym
TRAIN HFpEF
Official Title
Implementation, Safety, Tolerability and Effect of Exercise and Respiratory Training on 6-minute Walking Distance in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (HFpEF): a Randomized Controlled Multicenter Trial in European Countries.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 1, 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Exercise interventions alone or as a component of a comprehensive cardiac rehabilitation program for patients with heart failure (HFrEF and HFpEF) have already shown to reduce the risk of hospitalisations due to HF and improved exercise capacity and health-related quality of life. Two meta-analyses have confirmed the beneficial effects in cardiorespiratory fitness and quality of life. The effects of exercise training on systolic and diastolic function remain inconclusive. Due to the positive results of exercise training in HFpEF, cardiac rehabilitation is recommended (Class I, level A) to be integrated into the overall provision of HF care. However, none of these studies focused on concomitant PH in HFpEF. Exercise training in patients with pulmonary hypertension has already shown to improve exercise capacity, quality of life and peak oxygen consumption, which was confirmed by three meta-analyses and a Cochrane review. Though different diagnostic subgroups have already been enrolled in PH exercise training studies, they mainly included pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Data on combined PH and HFpEF is still lacking. As recently pointed out by Arena et al. there may thus be an exercise training volume/intensity which may be detrimental to the RV in patients with HF and concomitant PH. This study is sought to investigate whether a specialized training program is safe and tolerable and may improve exercise capacity, quality of life, hemodynamics, diastolic dysfunction and biomarkers in patients with PH and HFpEF.
Detailed Description
During the 6th World Symposium of PH in Nice, three main entities of PH due to left heart disease (PH-LHD) were identified. 1. PH due to HFpEF, 2. PH due to HF with reduced EF (HFrEF) and 3. PH due to valvular disease. The hemodynamic criteria measured by right heart catheterisation (RHC) of PH-LHD include mean pulmonary arterial pressure (mPAP)>20 mmHg and pulmonary arterial wedge pressure (PAWP) >15 mmHg. The hallmark of HFpEF is an elevation in left-sided filling pressures. In some patients this leads to elevation of mean pulmonary arterial pressure as secondary pulmonary hypertension (PH). Pulmonary arterial pressure is a marker of the severity and chronicity of pulmonary venous congestion in HFpEF and in case of presence of PH, symptoms are more severe and the outcome is poorer. Recently, an updated diagnostic algorithm (HFA-PEFF) for HFpEF was published as consensus recommendation from the Heart Failure Association of the European Society of Cardiology. In first step, a pre-test assessment is performed (P: Pretest). In case risk factors for HFpEF are existing electrocardiographic and echocardiographic evaluation as well as an exercise test are required. If the 1st step is proved positive, a detailed echocardiography (E: echocardiography) should be performed. A definite diagnosis of HFpEF can be made by right heart catheterization with PAWP ≥15mmHg or LVEDP ≥16mmHg at rest and/or PAWP ≥25mmHg during exercise in presence of preserved left ventricular function. Exercise interventions alone or as a component of a comprehensive cardiac rehabilitation program for patients with heart failure (HFrEF and HFpEF) have already shown to reduce the risk of hospitalisations due to HF and improved exercise capacity and health-related quality of life . Two meta-analyses have confirmed the beneficial effects in cardiorespiratory fitness and quality of life. The effects of exercise training on systolic and diastolic function remain inconclusive. Due to the positive results of exercise training in HFpEF, cardiac rehabilitation is recommended (Class I, level A) to be integrated into the overall provision of HF care. However, none of these studies focused on concomitant PH in HFpEF. Exercise training in patients with pulmonary hypertension has already shown to improve exercise capacity, quality of life and peak oxygen consumption, which was confirmed by three meta-analyses and a Cochrane review. Though different diagnostic subgroups have already been enrolled in PH exercise training studies, they mainly included pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Data on combined PH and HFpEF is still lacking. In healthy subjects, intensive exercise has already shown to cause potentially deleterious remodeling of the RV. As recently pointed out by Arena et al. there may thus be an exercise training volume/intensity which may be detrimental to the RV in patients with HF and concomitant PH. This study is sought to investigate whether a specialized training program is safe and tolerable and may improve exercise capacity, quality of life, hemodynamics, diastolic dysfunction and biomarkers in patients with PH and HFpEF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension Due to Left Heart Disease, Heart Failure With Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomised, controlled, parallel-group with crossover of the control group
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Exercise training
Arm Type
Active Comparator
Arm Title
Standard treatment (waiting group)
Arm Type
Placebo Comparator
Intervention Type
Other
Intervention Name(s)
Exercise rehabilitation
Intervention Description
The initial phase of exercise training will be closely monitored and will be based on a three-weeks in-hospital stay to adjust and teach the exercise training which will be continued at home for 12 more weeks. In-hospital stays will be arranged country specific and hospitalization time may range. The rehabilitation program comprises of interval ergometer training (20 minutes 5 days per week), dumbbell training (30 minutes 5 days per week), respiratory therapy (30 minutes 5 days per week), mental training and guided walks for 2-5 times/week.
Intervention Type
Other
Intervention Name(s)
Standard treatment
Intervention Description
Standard treatment during study duration
Primary Outcome Measure Information:
Title
6-minute walking distance
Time Frame
baseline to 15 weeks
Secondary Outcome Measure Information:
Title
WHO functional class
Time Frame
baseline to 15 weeks
Title
Quality of life physical component scale SF-36
Time Frame
baseline to 15 weeks
Title
Quality of life mental component scale SF-36
Time Frame
baseline to 15 weeks
Title
peak oxygen consumption
Time Frame
baseline to 15 weeks
Title
peak oxygen consumption/kg body weight
Time Frame
baseline to 15 weeks
Title
workload achieved during cardiopulmonary exercise testing
Time Frame
baseline to 15 weeks
Title
NT-proBNP (N-terminal pro brain natriuretic peptide)
Time Frame
baseline to 15 weeks
Title
Tricuspid annular plane systolic excursion
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Systolic pulmonary arterial pressure
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Right atrial area
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Right ventricular area
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Right ventricular pump function
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Left ventricular pump function
Description
echocardiography
Time Frame
baseline to 15 weeks
Title
Left ventricular eccentricity index
Description
echocardiography
Time Frame
baseline to 15 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female and male patients ≥18 years WHO/NYHA functional class II - IV PH with HFpEF diagnosed by right heart catheterisation showing: mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest; pulmonary arterial wedge pressure (PAWP) ≥15mmHg at rest or LVEDP ≥16mmHg and/or PAWP≥25 mmHg during exercise, and Preserved left ventricular ejection fraction ≥50% Patients receiving optimized therapy including intensified treatment with diuretics and who have been stable for 1 month before entering the study. Except for diuretics, medical treatment should not be changed during the study period. Able to understand and willing to sign the Informed Consent Form Exclusion Criteria: Pre-capillary pulmonary hypertension (Group I; Group III; Group IV; Group V according to PH guidelines) Congenital or acquired severe valvular diseases (severe aortic stenosis or insufficiency, severe mitral valve stenosis or insufficiency) Pregnancy or lactation Walking disability Subject who participates in an interventional study during the course of this study Severe lung disease: FEV1/FVC <0.5 and total lung capacity <60% of the normal value Active myocarditis, unstable angina pectoris, exercise induced ventricular arrhythmias, active liver disease, porphyria or elevations of serum transaminases >3 x ULN (upper limit of normal) or bilirubin >1.5 x ULN Haemoglobin concentration less than 75% of the lower limit of normal Systolic blood pressure <85 mmHg History or suspicion of inability to cooperate adequately.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ekkehard Grünig, MD
Phone
+496221396
Ext
1288
Email
ekkehard.gruenig@med.uni-heidelberg.de
First Name & Middle Initial & Last Name or Official Title & Degree
Nicola Benjamin, MSc
Phone
+49 6221 396
Ext
1288
Email
nicola.benjamin@med.uni-heidelberg.de
Facility Information:
Facility Name
Centre for Pulmonary Hypertension at the Thoraxklinik Heidelberg, Heidelberg University Hospital
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ekkehard Grünig, MD
Phone
+496221396
Ext
8053
Email
ekkehard.gruenig@med.uni-heidelberg.de
First Name & Middle Initial & Last Name & Degree
Ekkehard Grünig, MD
Facility Name
Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
City
Vilnius
Country
Lithuania
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Egle Paleviciute

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Training in HFpEF-PH

We'll reach out to this number within 24 hrs