Pulmonary Hypertension Due to Left Heart DiseaseTRAIN HFpEFNCT05464238
Training in HFpEF-PH
A study testing Exercise rehabilitation and Standard treatment in people with Pulmonary Hypertension Due to Left Heart Disease and Heart Failure With Preserved Ejection Fraction, run by Heidelberg University at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension Due to Left Heart Disease, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Exercise rehabilitation and Standard treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Feb 2023to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Germany1 site
Centre for Pulmonary Hypertension at the Thoraxklinik Heidelberg, Heidelberg University Hospital
Heidelberg, 69126
Ekkehard Grünig, MD, +496221396 ext. 8053, ekkehard.gruenig@med.uni-heidelberg.de
Ekkehard Grünig, MD
Lithuania1 site
Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Vilnius
Egle Paleviciute
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Pulmonary Hypertension Due to Left Heart Disease, Heart Failure With Preserved Ejection Fraction
- Being tested
- Exercise rehabilitation, Standard treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise rehabilitationOther
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.
Standard treatmentOther
Standard treatment during study duration
| Study group | Role | What they receive |
|---|---|---|
| Exercise training | Active comparator | Not described Receives: Other: Exercise rehabilitation |
| Standard treatment (waiting group) | Placebo comparator | Not described Receives: Other: Standard treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-minute walking distance
Measured: baseline to 15 weeks
Secondary outcomes (14)
WHO functional class
Measured: baseline to 15 weeks
Quality of life physical component scale SF-36
Measured: baseline to 15 weeks
Quality of life mental component scale SF-36
Measured: baseline to 15 weeks
peak oxygen consumption
Measured: baseline to 15 weeks
peak oxygen consumption/kg body weight
Measured: baseline to 15 weeks
workload achieved during cardiopulmonary exercise testing
Measured: baseline to 15 weeks
NT-proBNP (N-terminal pro brain natriuretic peptide)
Measured: baseline to 15 weeks
Tricuspid annular plane systolic excursion
echocardiography
Measured: baseline to 15 weeks
Systolic pulmonary arterial pressure
echocardiography
Measured: baseline to 15 weeks
Right atrial area
echocardiography
Measured: baseline to 15 weeks
Right ventricular area
echocardiography
Measured: baseline to 15 weeks
Right ventricular pump function
echocardiography
Measured: baseline to 15 weeks
Left ventricular pump function
echocardiography
Measured: baseline to 15 weeks
Left ventricular eccentricity index
echocardiography
Measured: baseline to 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study start1 Feb 2023 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Hypertension Due to Left Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised, controlled, parallel-group with crossover of the control group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. med. Ekkehard Gruenig, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05464238
- Sponsor's protocol ID
- 2019-04ET
- Acronym
- TRAIN HFpEF
- Status last verified
- Sep 2022
- First submitted
- 14 Jul 2022
- Last updated
- 16 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Paleviciute E, Celutkiene J, Simbelyte T, Gumbiene L, Jureviciene E, Zakarkaite D, Cesna S, Eichstaedt CA, Benjamin N, Grunig E. Safety and effectiveness of standardized exercise training in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (TRAIN-HFpEF-PH): study protocol for a randomized controlled multicenter trial. Trials. 2023 Apr 19;24(1):281. doi: 10.1186/s13063-023-07297-x.
PubMed 37072812
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05464238
- Acronym / sponsor ID
- TRAIN HFpEF / 2019-04ET
- Conditions
- Pulmonary Hypertension Due to Left Heart Disease, Heart Failure With Preserved Ejection Fraction
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- 1 Feb 2023 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised, controlled, parallel-group with crossover of the control group
| Arm | Type | Receives |
|---|---|---|
| Exercise training | Active comparator | Other: Exercise rehabilitation |
| Standard treatment (waiting group) | Placebo comparator | Other: Standard treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise rehabilitationThe 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. | Other | Exercise training |
| Standard treatmentStandard treatment during study duration | Other | Standard treatment (waiting group) |
Primary outcome
6-minute walking distance
Time frame: baseline to 15 weeks
14 secondary outcomes
WHO functional class
Time frame: baseline to 15 weeks
Quality of life physical component scale SF-36
Time frame: baseline to 15 weeks
Quality of life mental component scale SF-36
Time frame: baseline to 15 weeks
peak oxygen consumption
Time frame: baseline to 15 weeks
peak oxygen consumption/kg body weight
Time frame: baseline to 15 weeks
workload achieved during cardiopulmonary exercise testing
Time frame: baseline to 15 weeks
NT-proBNP (N-terminal pro brain natriuretic peptide)
Time frame: baseline to 15 weeks
Tricuspid annular plane systolic excursion
Time frame: baseline to 15 weeks
Systolic pulmonary arterial pressure
Time frame: baseline to 15 weeks
Right atrial area
Time frame: baseline to 15 weeks
Right ventricular area
Time frame: baseline to 15 weeks
Right ventricular pump function
Time frame: baseline to 15 weeks
Left ventricular pump function
Time frame: baseline to 15 weeks
Left ventricular eccentricity index
Time frame: baseline to 15 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2022.
- Derived from this study: PubMed 37072812Paleviciute E, Celutkiene J, Simbelyte T, Gumbiene L, Jureviciene E, Zakarkaite D, Cesna S, Eichstaedt CA, Benjamin N, Grunig E. Safety and effectiveness of standardized exercise training in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (TRAIN-HFpEF-PH): study protocol for a randomized controlled multicenter trial. Trials. 2023 Apr 19;24(1):281. doi: 10.1186/s13063-023-07297-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise rehabilitation and Standard treatment in people with Pulmonary Hypertension Due to Left Heart Disease and Heart Failure With Preserved Ejection Fraction, run by Heidelberg University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 16 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Lithuania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ekkehard Grünig, MD (+496221396 ext. 1288, ekkehard.gruenig@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-minute walking distance (time frame: baseline to 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05464238, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2022.