Heart Failure, DiastolicPhase 3NCT01726049
Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH
A Phase 3 study testing Sildenafil in people with Heart Failure, Diastolic and Pulmonary Hypertension, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of cardiac output (CO) and in improvement of exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension ( PH). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Diastolic, Pulmonary Hypertension
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2011to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- >18 years
- Written inform consent
- PH secondary to diastolic left heart failure defined as
- PAP mean >25 mmHg
- Wedge mean >15 mmHg
- Normal systolic left ventricular (LV) function on echo/nuclear imaging (left ventricular ejection fraction (LVEF) > or =45%)
- New York Heart Association class (NYHA) II-IV despite heart failure therapy
Who cannot join
- Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
- Other cause of PH besides diastolic heart failure
- Coronary ischemia or recent myocardial infarction (<6 months)
- Hypotension ( <90/50 mmHg)
- Ongoing nitrate therapy
- Ongoing therapy with citochrome P450 3A4 ( CYP3A4) inhibitors (ketoconazole, erythromycin, cimetidine, clarithromycin, itraconazole, voriconazole and protease inhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin, Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juice while on study medication because of the known impact of grape fruit on pharmacokinetics of Sildenafil.
Show all 11Show fewer
- Ongoing therapy with alpha -inhibitors
- Significant mitral or aortic valve dysfunction
- Severe liver dysfunction
- Pregnancy
- Unable to read and comprehend Dutch language
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Sildenafil on Pulmonary Arterial Pressure in Patients With Heart Failure With Preserved Ejection Fraction ( HFpEF) and Pulmonary Hypertension
Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of cardiac output (CO) and in improvement of exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension ( PH).
Read the detailed description
Rationale: Treatment of diastolic left heart failure is a challenging task. Compared to systolic left heart failure the level of evidence for known medical treatment regiments is low. Sildenafil, a phosphodiesterase 5 (PDE 5) inhibitor and effective therapy for pulmonary arterial hypertension acts as a selective pulmonary vasodilator by inhibiting the impaired nitric oxide (NO) pathway. Reducing the pulmonary vascular resistance would be the primary target by treatment of diastolic left heart failure with PH. But clinical and hemodynamical studies to evaluate the role of Sildenafil in diastolic heart failure, also called heart failure with preserved ejection fraction (HFpEF) with secondary pulmonary hypertension are lacking. Our hypothesis is that Sildenafil decreases pulmonary artery pressure in patients with HFpEF and pulmonary hypertension.
Objective: To investigate whether Sildenafil treatment results in a hemodynamic improvement and in an improvement of exercise capacity in these patients.
Study design: single-center, prospective, randomized, placebo controlled study. Study population: 52 patients with HFpEF and PH Intervention : One group receives three times daily 20 mg Sildenafil for 2 weeks followed by three times daily 60 mg Sildenafil for 10 weeks. The other group receives three times daily 20 mg of Placebo, followed by 3 times daily 60 mg placebo.
Main study parameters/endpoints:
Primary objectives
- To investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure (PAP) in HFpEF patients with PH (investigated invasively by right heart catheterization) .
Secondary objectives
- To investigate whether Sildenafil treatment results in an reduction of wedge pressure in HFpEF patients.
- To investigate whether Sildenafil treatment results in an improvenemt of cardiac output (CO) in HFpEF patients.
- To investigate whether Sildenafil treatment results in improvement of exercise capacity in these patients ( defined as change in VO2max)
- Conditions
- Heart Failure, Diastolic, Pulmonary Hypertension
- Being tested
- Sildenafil, Placebo
- Keywords
- HFpEF, PH
- Medical subject headings
- Heart Failure, Diastolic, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks
PlaceboDrug
Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Active comparator | Sildenafil orally 3 times 20mg for 2 weeks , followed by 3 times 60 mg for 10 weeks Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | placebo orally 3 times 20mg tablets, followed by 3 times 60 mg for 10 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization
change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation
Measured: baseline and 12 weeks
Secondary outcomes (3)
VO2max
difference in change of VO2 max between baseline and 12 weeks between Sildenafil and placebo group
Measured: baseline and 12 weeks
Cardiac Output Measured Invasively by Right Heart Catheterization
difference in change of cardiac output between baseline and 12 weeks between Sildenafil and Placebo group
Measured: baseline and 12 weeks
Wedge Pressure Measured Invasively by Right Heart Catheterization
Difference in change of wedge pressure between baseline and 12 weeks between Sildenafil group and Placebo group
Measured: baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2012 (estimated)
- Study startOct 2011
- Primary completionSep 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, E.S. Hoendermis, University Medical Center Groningen
- Investigators
- E S Hoendermis, MD PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01726049
- Sponsor's protocol ID
- Sildenafil Groningen Study
- Status last verified
- Feb 2016
- First submitted
- 21 Sep 2012
- Last updated
- 21 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Liu LC, Hummel YM, van der Meer P, Berger RM, Damman K, van Veldhuisen DJ, Voors AA, Hoendermis ES. Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension. Eur J Heart Fail. 2017 Jan;19(1):116-125. doi: 10.1002/ejhf.662. Epub 2016 Nov 21.
PubMed 27873388Hoendermis ES, Liu LC, Hummel YM, van der Meer P, de Boer RA, Berger RM, van Veldhuisen DJ, Voors AA. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J. 2015 Oct 7;36(38):2565-73. doi: 10.1093/eurheartj/ehv336. Epub 2015 Jul 17.
PubMed 26188003
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sildenafil on Pulmonary Arterial Pressure in Patients With Heart Failure With Preserved Ejection Fraction ( HFpEF) and Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT01726049
- Acronym / sponsor ID
- Sildenafil Groningen Study
- Conditions
- Heart Failure, Diastolic, Pulmonary Hypertension
- Keywords
- HFpEF, PH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Oct 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 14 Nov 2012 (estimated)
- Results
- Posted 21 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of cardiac output (CO) and in improvement of exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension ( PH).
Detailed description
Rationale: Treatment of diastolic left heart failure is a challenging task. Compared to systolic left heart failure the level of evidence for known medical treatment regiments is low. Sildenafil, a phosphodiesterase 5 (PDE 5) inhibitor and effective therapy for pulmonary arterial hypertension acts as a selective pulmonary vasodilator by inhibiting the impaired nitric oxide (NO) pathway. Reducing the pulmonary vascular resistance would be the primary target by treatment of diastolic left heart failure with PH. But clinical and hemodynamical studies to evaluate the role of Sildenafil in diastolic heart failure, also called heart failure with preserved ejection fraction (HFpEF) with secondary pulmonary hypertension are lacking. Our hypothesis is that Sildenafil decreases pulmonary artery pressure in patients with HFpEF and pulmonary hypertension.
Objective: To investigate whether Sildenafil treatment results in a hemodynamic improvement and in an improvement of exercise capacity in these patients.
Study design: single-center, prospective, randomized, placebo controlled study. Study population: 52 patients with HFpEF and PH Intervention : One group receives three times daily 20 mg Sildenafil for 2 weeks followed by three times daily 60 mg Sildenafil for 10 weeks. The other group receives three times daily 20 mg of Placebo, followed by 3 times daily 60 mg placebo.
Main study parameters/endpoints:
Primary objectives
- To investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure (PAP) in HFpEF patients with PH (investigated invasively by right heart catheterization) .
Secondary objectives
- To investigate whether Sildenafil treatment results in an reduction of wedge pressure in HFpEF patients.
- To investigate whether Sildenafil treatment results in an improvenemt of cardiac output (CO) in HFpEF patients.
- To investigate whether Sildenafil treatment results in improvement of exercise capacity in these patients ( defined as change in VO2max)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Active comparator | Drug: SildenafilSildenafil orally 3 times 20mg for 2 weeks , followed by 3 times 60 mg for 10 weeks |
| Placebo | Placebo comparator | Drug: Placeboplacebo orally 3 times 20mg tablets, followed by 3 times 60 mg for 10 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- >18 years
- Written inform consent
- PH secondary to diastolic left heart failure defined as
- PAP mean >25 mmHg
- Wedge mean >15 mmHg
Key exclusion criteria (11 listed)
- Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
- Other cause of PH besides diastolic heart failure
- Coronary ischemia or recent myocardial infarction (<6 months)
- Hypotension ( <90/50 mmHg)
- Ongoing nitrate therapy
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 |
|---|---|---|
| SildenafilSildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks | Drug | Sildenafil |
| PlaceboPlacebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks | Drug | Placebo |
Primary outcome
Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization
Time frame: baseline and 12 weeks
change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation
3 secondary outcomes
VO2max
Time frame: baseline and 12 weeks
Cardiac Output Measured Invasively by Right Heart Catheterization
Time frame: baseline and 12 weeks
Wedge Pressure Measured Invasively by Right Heart Catheterization
Time frame: baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27873388Liu LC, Hummel YM, van der Meer P, Berger RM, Damman K, van Veldhuisen DJ, Voors AA, Hoendermis ES. Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension. Eur J Heart Fail. 2017 Jan;19(1):116-125. doi: 10.1002/ejhf.662. Epub 2016 Nov 21.
- Derived from this study: PubMed 26188003Hoendermis ES, Liu LC, Hummel YM, van der Meer P, de Boer RA, Berger RM, van Veldhuisen DJ, Voors AA. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J. 2015 Oct 7;36(38):2565-73. doi: 10.1093/eurheartj/ehv336. Epub 2015 Jul 17.
Related trials for Heart Failure, Diastolic
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 1
A Study of LY3971297 in Participants With Heart Failure
Heart Failure, Heart Failure, Diastolic
Not yet recruiting
Importance of Point-of-Care Ultrasound for Early Detection of Valvular and Cardiac Diseases (IMPROVE)
Valvular Heart Disease Patients, Aortic Stenosis
Recruiting
PrEcision Pacing in HFpEF: the PEP-HFpEF Trial
Heart Failure and Preserved Ejection Fraction, Heart Failure New York Heart Association Class III
Recruiting
Assessment of CCM in HF With Higher Ejection Fraction
Heart Failure, Heart Failure With Preserved Ejection Fraction
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. This study is not recruiting at the moment.
E S Hoendermis, MD PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil in people with Heart Failure, Diastolic and Pulmonary Hypertension, run by University Medical Center Groningen at 1 site in Netherlands.
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 7 inclusion and 11 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: finished, as of the sponsor's last update on 21 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization (time frame: baseline and 12 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 NCT01726049, which also lists 2 linked publications.
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 21 Mar 2016; AzTrials last refreshed its copy on 7 Nov 2026.