Heart FailurePhase 3NCT00975494
Chronic Sildenafil Treatment in Heart Failure
A Phase 3 study testing Sildenafil in people with Heart Failure, run by University of Milan at 2 sites in Italy.
Trial summary
In heart failure (HF), a defective nitric oxide (NO) signaling may be involved in left ventricular (LV) diastolic abnormalities and LV remodelling progression. PDE5-inhibition, by blocking NO degradation and overexpressing cellular cyclic guanosine monophosphate (cGMP) pathways might be beneficial. Read more about this study
- Who is it for?
- Ages 38 to 80 years, men only
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesItaly
- Study dates
- Apr 2005to Dec 2008
- Phase
- Phase 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 38 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- consent to participate in the study after detailed information about procedures, possible clinical benefits and risks;
- negative exercise stress test prior to study initiation;
- forced expiratory volume in 1 sec/forced vital capacity ratio>70%;
- left ventricular ejection fraction < 45%, determined by echocardiography.
Who cannot join
- subjects unable to complete a maximal exercise test
- systolic blood pressure > 140 and <110 mmHg
- diabetes mellitus
- therapy with nitrate preparations
- history of sildenafil intolerance
- significant lung or valvular diseases
- neuromuscular disorders, claudication
- peripheral vascular disease
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Chronic PDE5-Inhibition With Sildenafil Improves Diastolic Function, Cardiac Geometry and Clinical Status in Patients With Stable HF: A 1-Year Prospective Randomized, Placebo-Controlled Study
In heart failure (HF), a defective nitric oxide (NO) signaling may be involved in left ventricular (LV) diastolic abnormalities and LV remodelling progression. PDE5-inhibition, by blocking NO degradation and overexpressing cellular cyclic guanosine monophosphate (cGMP) pathways might be beneficial. Several short term studies have demonstrated safety and clinical improvement in stable heart failure (HF) patients.
The purpose of this study is to test the effects on LV diastolic function, cardiac geometry and clinical status in a cohort of HF patients.
Read the detailed description
Heart failure (HF) is a significant health care concern that is evolving to epidemic proportions. Development of new forms of interventions remains a challenging task. An abnormal nitric oxide (NO) pathway is involved in several basic pathophysiological abnormalities encountered in HF syndrome and NO overexpression may represent a desirable therapeutic target in the cure of the disease.
PDE5-inhibition is an intriguing pharmacological strategy to enhance in vivo nitric oxide (NO) signaling by increasing the cyclic guanosine monophosphate (cGMP). availability. A number of theoretical backgrounds support the use of PDE5-inhibitors in HF and an increasing number of clinical studies have been testing PDE5-inhibition as a potential valid adjunct in the management of HF patients.
In failing hearts of animal models, PDE5-inhibition has also provided the attractive therapeutic properties to reverse left ventricular chamber remodelling by preventing and reversing LV cardiac hypertrophy and fibrosis and by protecting the myocardium from ischemia-reperfusion injury and apoptosis. There is also evidence that a defective NO activity plays an important role in the excitation-relaxation process of the failing heart, an effect explained by a defective cGMP-induced phosphorylation of troponin I, which facilitates calcium-independent diastolic cross-bridge cycling and concomitant myocardium diastolic stiffening.
No report has so far investigated whether cardiac function and, primarily, diastolic LV function may be a target of chronic PDE5-inhibition and whether any improvement in diastolic function is related to a reverse effect in cardiac geometry in patients with HF. Furthermore, it is undefined whether a favourable effect on left ventricular function may be involved in the reported changes in important clinical correlates such as functional status and quality of life. We tested these hypotheses, by addressing the effects of chronic sildenafil administration (50 mg three times/day) on diastolic function and clinical status by Tissue Doppler imaging, cardiopulmonary exercise testing and quality of life score.
- Conditions
- Heart Failure
- Being tested
- Sildenafil, Placebo
- Keywords
- pde5-inhibition, sildenafil, LV diastolic function, heart failure patients
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| sildenafil | Active comparator | sildenafil 50 mg three times/day Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular diastolic function
Measured: 1 year
Secondary outcomes (4)
Functional capacity
Measured: 1 year
Quality of life
Measured: 1 year
Neurohumoral (brain natriuretic peptide)
Measured: 1 year
Cardiac remodeling
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 posted11 Sep 2009 (estimated)
- Study startApr 2005
- Study completionDec 2008
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 Heart FailureStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00975494
- Sponsor's protocol ID
- 444-05
- Status last verified
- Sep 2009
- First submitted
- 3 Sep 2009
- Last updated
- 11 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011 Jan;4(1):8-17. doi: 10.1161/CIRCHEARTFAILURE.110.944694. Epub 2010 Oct 29.
PubMed 21036891
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic PDE5-Inhibition With Sildenafil Improves Diastolic Function, Cardiac Geometry and Clinical Status in Patients With Stable HF: A 1-Year Prospective Randomized, Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT00975494
- Acronym / sponsor ID
- 444-05
- Conditions
- Heart Failure
- Keywords
- pde5-inhibition, sildenafil, LV diastolic function, heart failure patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- Apr 2005
- Study completion
- Dec 2008 (actual)
- First posted
- 11 Sep 2009 (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.
In heart failure (HF), a defective nitric oxide (NO) signaling may be involved in left ventricular (LV) diastolic abnormalities and LV remodelling progression. PDE5-inhibition, by blocking NO degradation and overexpressing cellular cyclic guanosine monophosphate (cGMP) pathways might be beneficial. Several short term studies have demonstrated safety and clinical improvement in stable heart failure (HF) patients.
The purpose of this study is to test the effects on LV diastolic function, cardiac geometry and clinical status in a cohort of HF patients.
Detailed description
Heart failure (HF) is a significant health care concern that is evolving to epidemic proportions. Development of new forms of interventions remains a challenging task. An abnormal nitric oxide (NO) pathway is involved in several basic pathophysiological abnormalities encountered in HF syndrome and NO overexpression may represent a desirable therapeutic target in the cure of the disease.
PDE5-inhibition is an intriguing pharmacological strategy to enhance in vivo nitric oxide (NO) signaling by increasing the cyclic guanosine monophosphate (cGMP). availability. A number of theoretical backgrounds support the use of PDE5-inhibitors in HF and an increasing number of clinical studies have been testing PDE5-inhibition as a potential valid adjunct in the management of HF patients.
In failing hearts of animal models, PDE5-inhibition has also provided the attractive therapeutic properties to reverse left ventricular chamber remodelling by preventing and reversing LV cardiac hypertrophy and fibrosis and by protecting the myocardium from ischemia-reperfusion injury and apoptosis. There is also evidence that a defective NO activity plays an important role in the excitation-relaxation process of the failing heart, an effect explained by a defective cGMP-induced phosphorylation of troponin I, which facilitates calcium-independent diastolic cross-bridge cycling and concomitant myocardium diastolic stiffening.
No report has so far investigated whether cardiac function and, primarily, diastolic LV function may be a target of chronic PDE5-inhibition and whether any improvement in diastolic function is related to a reverse effect in cardiac geometry in patients with HF. Furthermore, it is undefined whether a favourable effect on left ventricular function may be involved in the reported changes in important clinical correlates such as functional status and quality of life. We tested these hypotheses, by addressing the effects of chronic sildenafil administration (50 mg three times/day) on diastolic function and clinical status by Tissue Doppler imaging, cardiopulmonary exercise testing and quality of life score.
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 50 mg three times/day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 38 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- consent to participate in the study after detailed information about procedures, possible clinical benefits and risks;
- negative exercise stress test prior to study initiation;
- forced expiratory volume in 1 sec/forced vital capacity ratio>70%;
- left ventricular ejection fraction < 45%, determined by echocardiography.
Key exclusion criteria (8 listed)
- subjects unable to complete a maximal exercise test
- systolic blood pressure > 140 and <110 mmHg
- diabetes mellitus
- therapy with nitrate preparations
- history of sildenafil intolerance
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 |
|---|---|---|
| Sildenafil | Drug | sildenafil |
| Placebo | Drug | Placebo |
Primary outcome
Left ventricular diastolic function
Time frame: 1 year
4 secondary outcomes
Functional capacity
Time frame: 1 year
Quality of life
Time frame: 1 year
Neurohumoral (brain natriuretic peptide)
Time frame: 1 year
Cardiac remodeling
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 11 Sep 2009.
- Derived from this study: PubMed 21036891Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011 Jan;4(1):8-17. doi: 10.1161/CIRCHEARTFAILURE.110.944694. Epub 2010 Oct 29.
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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.
2 sites 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, run by University of Milan at 2 sites in Italy.
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 4 inclusion and 8 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 11 Sep 2009. 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 Italy. 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?
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?
Left ventricular diastolic function (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 NCT00975494, 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 11 Sep 2009.