Pulmonary HypertensionPhase 2/3NCT01156636
Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure
A Phase 2/3 study testing Sildenafil in people with Pulmonary Hypertension and Diastolic Heart Failure, run by University of Milan.
Trial summary
Prevalence of heart failure (HF) with left ventricular (LV) diastolic dysfunction and preserved ejection fraction (EF) (HFpEF) is increasing. Prognosis worsens with development of pulmonary vasoconstriction and hypertension (PH) and right ventricular (RV) failure. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Pulmonary Hypertension, Diastolic Heart Failure
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- Jan 2006to Dec 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- LVEF >50%
- sinus rhythm and stable clinical condition defined as no changes in therapeutic regimen, or hospitalization in the 6 months preceding recruitment.
- pulmonary artery systolic pressure > 40 mm Hg,
Who cannot join
- Patients receiving nitrates
- A history of pulmonary disease
- Alternative causes of PH other than cardiac-related
- Renal failure (creatinine > 2mg/dL)
- Anemia
- Pericardial disease
- Cardiac amyloidosis
About this study
Official title: Pulmonary Hypertension Secondary to Heart Failure With Preserved Systolic Function: a Target of Phosphodiesterase - 5 Inhibition in a 1- Year Duration Study
Prevalence of heart failure (HF) with left ventricular (LV) diastolic dysfunction and preserved ejection fraction (EF) (HFpEF) is increasing. Prognosis worsens with development of pulmonary vasoconstriction and hypertension (PH) and right ventricular (RV) failure. The investigators aimed at modulating pulmonary vascular tone and RV burden in HFpEF due to high blood pressure (HBP), by using the phosphodiesterase-5 (PDE5) inhibitor sildenafil.
Read the detailed description
Heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) is a public health problem and a major topic in clinical cardiology. Its prevalence, in fact, is increasing and the outcome seems to be similar to that of HF with LV systolic dysfunction (LVSD). Pulmonary hypertension (PH) in HFpEF is highly prevalent and often severe and, like in LVSD (3), is a predictor of morbidity and mortality (4). Because of the thin wall and the distensibility, the right ventricle (RV) is much more vulnerable by an excessive afterload than by preload. The pulmonary circulation is a central determinant of RV afterload, and an increase in impendance to RV ejection, like occurring in LV dysfunction, can easily result in RV failure, tricuspid regurgitation, central venous pressure (CVP) rise. Development of RV failure is unanimously viewed as a predictor of poor prognosis but the underlying mechanisms have not been extensively investigated.
Because of the prevalence and clinical significance of PH secondary to HF, attenuation of the pulmonary vascular tone and of the RV hemodynamic burden has been suggested as a goal to be achieved with HF therapy. Attempts with endothelin receptor antagonists, or prostacyclin analogues, were basically unsuccessful. Experimental models and human studies, showing that in HF nitric oxide (NO) - dependent pulmonary vasodilatation is impaired and pulmonary vascular resistance elevation is at least in part due to pulmonary endothelial dysfunction, have suggested therapeutic strategies with agents that increase NO activity, like nitrates or phosphodiesterase - 5 (PDE5) inhibitors (12-14). The latter agents offer the double advantage of selectively dilating the pulmonary vessels and not producing tachyphylaxis.
In this 1-year duration study, the primary end-point was to probe whether pulmonary hemodynamics and RV performance in HFpEF with PH may be targets of PDE5 inhibition with sildenafil.
- Conditions
- Pulmonary Hypertension, Diastolic Heart Failure
- Being tested
- Sildenafil, Placebo
- Keywords
- Diastolic Heart Failure, Pulmonary Hypertension
- Medical subject headings
- Hypertension, Pulmonary, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
50 mg 3 times/day for 1 year
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Active comparator | Not described Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary hemodynamics
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2010 (estimated)
- Study startJan 2006
- Primary completionSep 2009
- Study completionDec 2009
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 HypertensionStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01156636
- Sponsor's protocol ID
- 444-10
- Status last verified
- Jun 2009
- First submitted
- 2 Jul 2010
- Last updated
- 15 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011 Jul 12;124(2):164-74. doi: 10.1161/CIRCULATIONAHA.110.983866. Epub 2011 Jun 27.
PubMed 21709061
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Hypertension Secondary to Heart Failure With Preserved Systolic Function: a Target of Phosphodiesterase - 5 Inhibition in a 1- Year Duration Study
- ClinicalTrials.gov ID
- NCT01156636
- Acronym / sponsor ID
- 444-10
- Conditions
- Pulmonary Hypertension, Diastolic Heart Failure
- Keywords
- Diastolic Heart Failure, Pulmonary Hypertension
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 5 Jul 2010 (estimated)
- 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.
Prevalence of heart failure (HF) with left ventricular (LV) diastolic dysfunction and preserved ejection fraction (EF) (HFpEF) is increasing. Prognosis worsens with development of pulmonary vasoconstriction and hypertension (PH) and right ventricular (RV) failure. The investigators aimed at modulating pulmonary vascular tone and RV burden in HFpEF due to high blood pressure (HBP), by using the phosphodiesterase-5 (PDE5) inhibitor sildenafil.
Detailed description
Heart failure (HF) with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) is a public health problem and a major topic in clinical cardiology. Its prevalence, in fact, is increasing and the outcome seems to be similar to that of HF with LV systolic dysfunction (LVSD). Pulmonary hypertension (PH) in HFpEF is highly prevalent and often severe and, like in LVSD (3), is a predictor of morbidity and mortality (4). Because of the thin wall and the distensibility, the right ventricle (RV) is much more vulnerable by an excessive afterload than by preload. The pulmonary circulation is a central determinant of RV afterload, and an increase in impendance to RV ejection, like occurring in LV dysfunction, can easily result in RV failure, tricuspid regurgitation, central venous pressure (CVP) rise. Development of RV failure is unanimously viewed as a predictor of poor prognosis but the underlying mechanisms have not been extensively investigated.
Because of the prevalence and clinical significance of PH secondary to HF, attenuation of the pulmonary vascular tone and of the RV hemodynamic burden has been suggested as a goal to be achieved with HF therapy. Attempts with endothelin receptor antagonists, or prostacyclin analogues, were basically unsuccessful. Experimental models and human studies, showing that in HF nitric oxide (NO) - dependent pulmonary vasodilatation is impaired and pulmonary vascular resistance elevation is at least in part due to pulmonary endothelial dysfunction, have suggested therapeutic strategies with agents that increase NO activity, like nitrates or phosphodiesterase - 5 (PDE5) inhibitors (12-14). The latter agents offer the double advantage of selectively dilating the pulmonary vessels and not producing tachyphylaxis.
In this 1-year duration study, the primary end-point was to probe whether pulmonary hemodynamics and RV performance in HFpEF with PH may be targets of PDE5 inhibition with sildenafil.
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: Sildenafil |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- LVEF >50%
- sinus rhythm and stable clinical condition defined as no changes in therapeutic regimen, or hospitalization in the 6 months preceding recruitment.
- pulmonary artery systolic pressure > 40 mm Hg,
Key exclusion criteria (7 listed)
- Patients receiving nitrates
- A history of pulmonary disease
- Alternative causes of PH other than cardiac-related
- Renal failure (creatinine > 2mg/dL)
- Anemia
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 |
|---|---|---|
| Sildenafil50 mg 3 times/day for 1 year | Drug | Sildenafil |
| Placebo | Drug | Placebo |
Primary outcome
Pulmonary hemodynamics
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2012.
- Derived from this study: PubMed 21709061Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011 Jul 12;124(2):164-74. doi: 10.1161/CIRCULATIONAHA.110.983866. Epub 2011 Jun 27.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sildenafil in people with Pulmonary Hypertension and Diastolic Heart Failure, run by University of Milan.
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 3 inclusion and 7 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 15 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pulmonary hemodynamics (time frame: 1 year). 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 NCT01156636, 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 15 Jun 2012.