COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01156636
Recruitment Status : Completed
First Posted : July 5, 2010
Last Update Posted : June 15, 2012
Information provided by:
University of Milan

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Diastolic Heart Failure Drug: Sildenafil Drug: Placebo Phase 2 Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pulmonary Hypertension Secondary to Heart Failure With Preserved Systolic Function: a Target of Phosphodiesterase - 5 Inhibition in a 1- Year Duration Study
Study Start Date : January 2006
Actual Primary Completion Date : September 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Sildenafil Drug: Sildenafil
50 mg 3 times/day for 1 year

Placebo Comparator: Placebo Drug: Placebo

Primary Outcome Measures :
  1. Pulmonary hemodynamics [ Time Frame: 1 year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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,

Exclusion Criteria:

  • 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
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Milano, Cardiology (Marco Guazzi PI), University of Milano Identifier: NCT01156636    
Other Study ID Numbers: 444-10
First Posted: July 5, 2010    Key Record Dates
Last Update Posted: June 15, 2012
Last Verified: June 2009
Keywords provided by University of Milan:
Diastolic Heart Failure
Pulmonary Hypertension
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension, Pulmonary
Heart Failure
Heart Failure, Diastolic
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents