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

This study has been completed.
Sponsor:
Information provided by:
University of Milan
ClinicalTrials.gov Identifier:
NCT01156636
First received: July 2, 2010
Last updated: June 14, 2012
Last verified: June 2009
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Diastolic Heart Failure
Drug: Sildenafil
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Milan:

Primary Outcome Measures:
  • Pulmonary hemodynamics [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: January 2006
Study Completion Date: December 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sildenafil Drug: Sildenafil
50 mg 3 times/day for 1 year
Placebo Comparator: Placebo Drug: Placebo

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by University of Milan

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Milano, Cardiology (Marco Guazzi PI), University of Milano
ClinicalTrials.gov Identifier: NCT01156636     History of Changes
Other Study ID Numbers: 444-10
Study First Received: July 2, 2010
Last Updated: June 14, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by University of Milan:
Diastolic Heart Failure
Pulmonary Hypertension

Additional relevant MeSH terms:
Heart Failure
Hypertension
Hypertension, Pulmonary
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 28, 2014