Sildenafil for Vascular Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Montefiore Medical Center
Must not be taking: Nitric oxide donors
Disqualifiers: Aortic valve prosthesis, Aortic graft, Carotid occlusion, others
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?Contemporary left ventricular assist device (LVAD) therapy improves survival during advanced heart failure but vascular aging develops rapidly leading to major adverse events including stroke and bleeding in nearly half of patients. In this study, the study team aims to investigate whether sildenafil pharmacotherapy, which has anti-fibrotic effects, can reduce vascular aging during LVAD support. An aim of this study is to compare changes in small blood vessels in the gastrointestinal tract between participants receiving sildenafil or placebo. Video capsule endoscopy (VCE) will be used to assess these changes in small blood vessels.
Do I need to stop my current medications for the trial?
If you are taking any nitric oxide (NO) donor medications, you will need to stop them to participate in this trial.
What data supports the effectiveness of the drug sildenafil for vascular disease?
Sildenafil, known for treating erectile dysfunction, has shown promise in improving heart health by protecting against heart damage and lowering blood pressure in certain conditions. It is also effective in treating pulmonary arterial hypertension, a type of high blood pressure affecting the lungs.
12345Is sildenafil safe for use in humans?
Sildenafil, known by various brand names like Viagra and Revatio, is generally considered safe for most people, but it should not be used with nitrates (medications for chest pain) as this can cause a dangerous drop in blood pressure. Some reports have noted heart-related issues, especially in those with existing heart conditions, so it's important to consult a doctor if you have heart disease.
46789How is the drug sildenafil unique for treating vascular disease?
Sildenafil is unique for treating vascular disease because it not only helps with erectile dysfunction and pulmonary hypertension but also shows promise in protecting the heart from damage due to reduced blood flow and other cardiovascular issues. It works by inhibiting an enzyme called phosphodiesterase-5, which helps relax blood vessels and improve blood flow.
45101112Eligibility Criteria
This trial is for adults over 18 who are receiving durable left ventricular assist device (LVAD) support and can give informed consent. It's not suitable for those with a pre-existing aortic valve prosthesis or graft, allergy to sildenafil, complete carotid occlusion, or those taking nitric oxide donor medications.Inclusion Criteria
Durable left ventricular assist device support
Be able to give informed consent
I am over 18 years old.
Exclusion Criteria
History of pre-existing aortic valve prosthesis or an aortic graft
Allergy to sildenafil
I have had a complete blockage in my carotid artery.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sildenafil or placebo to assess vascular remodeling during LVAD support
180 days
Regular visits for monitoring and assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing if sildenafil can slow down vascular aging in patients with LVADs. Vascular aging often leads to strokes and bleeding. Participants will either receive sildenafil or a placebo without knowing which one they're getting.
2Treatment groups
Active Control
Placebo Group
Group I: SildeanfilActive Control1 Intervention
Participants in this arm will receive sildenafil 20mg every 8 hours for 1 week and then dose will be up titrated to 40mg every 8 hours for the duration of the study period.
Group II: PlaceboPlacebo Group1 Intervention
Participants in this arm will receive matching placebo, which serves as a negative control to understand changes in small and large blood vessels.
Sildenafil is already approved in United States, European Union, United States, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Viagra for:
- Erectile dysfunction
- Pulmonary arterial hypertension
🇪🇺 Approved in European Union as Viagra for:
- Erectile dysfunction
- Pulmonary arterial hypertension
🇺🇸 Approved in United States as Revatio for:
- Pulmonary arterial hypertension
🇨🇦 Approved in Canada as Sildenafil for:
- Erectile dysfunction
- Pulmonary arterial hypertension
🇯🇵 Approved in Japan as Sildenafil for:
- Erectile dysfunction
- Pulmonary arterial hypertension
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montefiore Medical CenterBronx, NY
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Who Is Running the Clinical Trial?
Montefiore Medical CenterLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Three-year update of sildenafil citrate (Viagra) efficacy and safety. [2022]In the three years since its launch, sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been prescribed to more than 10 million patients worldwide and has been further evaluated in clinical studies in diverse patient populations. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled trials in patients with ED and underlying diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. Promising results have also been reported for patients with treated prostate cancer, end-stage renal failure, Parkinson's disease, and spina bifida and in multiple organ transplant recipients. Accounts of sildenafil use in clinical practice and postmarketing data reflect clinical trial findings of effectiveness in a broad spectrum of ED aetiologies and overall good tolerability. As in the clinical trials, most adverse events associated with sildenafil use have been transient, mild or moderate effects that rarely lead to treatment discontinuation.
Cardiovascular effects of phosphodiesterase 5 inhibitors. [2019]Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are now approved for the treatment of erectile dysfunction. They inhibit the cGMP-specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which, for example in smooth muscle cells, reduces muscular tone. In the cardiovascular system, they slightly reduce arterial systemic blood pressure. This moderate effect was also shown in combination with many antihypertensive drugs. But the important contraindication is the concomitant use of PDE 5 inhibitors with any drug serving as a nitric oxide donor, as this combination can lead to significant arterial hypotension. Caution is needed in patients on alpha-blocking agents. In general, this class of drugs was not shown to exhibit direct deleterious effects on the myocardium or promote arrhythmias. Furthermore, statistical evaluations did not demonstrate an increased risk for patients taking PDE 5 inhibitors in comparison with an adequate control population. Many patients suffering from erectile dysfunction may be characterized by multiple cardiovascular risk factors or even ischemic heart disease, suggesting an increased baseline risk. While in many forms of erectile dysfunction, these agents seem to be very effective, it becomes clear that endothelial dysfunction is an attractive target of PDE 5 inhibitors and may also be the underlying cause in many types of erectile dysfunction. In addition, these agents seem to be very effective in lowering pulmonary arterial pressure, which might provide the opportunity to treat primary and some forms of secondary pulmonary hypertension, perhaps in combination with inhaled nitric oxide or other pulmonary arterial vasodilators. Sildenafil was approved for treatment of primary arterial hypertension in the U.S. in June 2005. Recently, direct cardioprotective effects were described in animal research, resembling preconditioning-like effects, which may, under certain conditions, also be applicable in clinical research.
Sildenafil: a review of its use in pulmonary arterial hypertension. [2021]Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
ALERT: Revatio is another brand name for sildenafil. [2017]In this column, the authors highlight a medication incident that occurred with Revatio (sildenafil), along with the learnings and recommendations from a previously published ISMP Canada Safety Bulletin. It is well-known to health care practitioners that use of nitroglycerin therapy is contraindicated in patients taking sildenafil (commonly known as Viagra). Many health care practitioners may be unaware that sildenafil is also marketed under the brand name Revatio for treatment of primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disease. The following incident signals the need to heighten the awareness that Revatio is a brand name for sildenafil.
Cardiovascular protection with sildenafil following chronic inhibition of nitric oxide synthase. [2018]During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.
[Side effects of sildenafil: findings from two years practical experience]. [2015]Sildenafil has been registered for the treatment of erectile dysfunction since 1998. World wide a large number of patients were reported, dying of acute heart disease after using sildenafil. Therefore the patient instruction text was adapted. Simultaneous use of sildenafil and nitrates is contraindicated because of serious decrease of the blood pressure. The use of sildenafil can lead to physical stress in patients with a history of heart disease and a treadmill test assessment is advisable. In two years 38 adverse reactions were seen in 25 Dutch patients. The Dutch reports (three cardiovascular deaths since the introduction) also show the dilemmas in the assessment of the safety of sildenafil: is it the underlying disease or is it the drug that causes death? Further research into the adverse reactions has to be done, therefore reporting suspected side effects of sildenafil is important.
Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. [2019]Adverse cardiac events in patients treated with the phosphodiesterase-5 inhibitor sildenafil for erectile dysfunction raised concerns about its safety in ischemic heart disease.
Cardiovascular safety of sildenafil. [2018]Initial reports of myocardial infarction and sudden death in men with erectile dysfunction who had taken sildenafil (sometimes in conjunction with nitrates) raised concerns that sildenafil may increase the risk of cardiovascular events in men with erectile dysfunction and vascular disease. A significant body of evidence now indicates that sildenafil generally has a good safety profile in men with erectile dysfunction and cardiovascular disease. Sildenafil therapy does not appear to be associated with ischaemic events either at the time of introduction of therapy or during longer-term use. Rates of discontinuation from sildenafil therapy due to adverse events are similar to placebo in men with cardiovascular disease. Sildenafil does not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of nitrates. Nitrates should not be administered within 24 hours of sildenafil therapy, and care should be taken to determine whether sildenafil may have been used before nitrates are administered to patients. Sildenafil appears to be generally well tolerated in most patients with chronic, stable cardiovascular disease.
Evaluation of the safety of sildenafil for male erectile dysfunction: experience gained in general practice use in England in 1999. [2015]To examine the safety of sildenafil, the first of the phosphodiesterase type 5 inhibitors licensed for the treatment of male erectile dysfunction (ED), as used in general medical practice in England, quantifying the incidence of a range of events in patients treated with sildenafil, and identifying any previously unrecognized adverse drug reactions.
Vardenafil: a new approach to the treatment of erectile dysfunction. [2019]Vardenafil is a phosphodiesterase type-5 (PDE-5) inhibitor developed as an oral therapy for erectile dysfunction (ED). Multiple phase 3 clinical trials have been completed and vardenafil is expected to launch worldwide in 2003. Two pivotal, randomized, double-blind, multicenter studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement also was noted in other aspects of sexual function, including confidence, orgasmic function, and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity, and etiology and is efficacious for the treatment of ED in diabetic and postprostatectomy patients. Vardenafil has a rapid onset of action and completion of successful sexual intercourse is possible for some patients 16 minutes after its administration. Twenty milligrams of vardenafil has sustained long-term efficacy by providing up to 92% of patients with improved erections during more than 2 years of treatment. Vardenafil is well tolerated, with an adverse event profile typical of the class of PDE-5 inhibitors. The most common adverse events were headache, flushing, rhinitis, and dyspepsia, which were mild or moderate and generally decreased with continued treatment. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo.
Sublingual application of liquid nitrendipine does not result in critical hypotension in healthy volunteers under phosphodiesterase-5 inhibition. [2015]The introduction of phosphodiesterase-5 inhibitors as sildenafil, tadalafil, or vardenafil, has tremendously improved the treatment of erectile dysfunction. Patients with the common comorbidity of cardiovascular disease and erectile dysfunction, however, are at risk for critical hypotension in case of self-treatment of cardiac angina with nitrates after the intake of a phosphodiesterase-5 inhibitor.
New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is). [2022]Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). In addition to this, sildenafil and tadalafil, have also been approved for the treatment of pulmonary arterial hypertension. Due to its expression and localization in many tissues, PDE5 and its regulation has been reported to be involved in several other diseases.