Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease - Full Text View

Sponsors and Collaborators:	Hospital General Universitario Gregorio Marañon Instituto de Salud Carlos III
Information provided by:	Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier:	NCT00862043

Purpose

The purpose of this study is to evaluate the clinical efficacy of the mid-term treatment with sildenafil in patients with persistent moderate or severe pulmonary hypertension (PH) after a heart valve intervention.

Condition	Intervention	Phase
Pulmonary Hypertension Valvular Heart Disease	Drug: Sildenafil Citrate Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Sildenafil for Improving Outcomes After Valvular Correction

Resource links provided by NLM:

MedlinePlus related topics: Heart Diseases Heart Failure Heart Valve Diseases High Blood Pressure Pulmonary Hypertension

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by Hospital General Universitario Gregorio Marañon:

Primary Outcome Measures:

Combined Outcome End-Point: all-cause mortality or hospital admission for heart failure, worsening of World Health Organization (WHO) functional class, or of the patient global assessment score [ Time Frame: Six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline to the sixth month in the in the six-minute walk test [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
Change on WHO functional capacity [ Time Frame: 3 & 6 Months ] [ Designated as safety issue: No ]
All cause mortality [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
Cardiovascular mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Number of hospital admissions caused by or related to heart failure in each patient [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Rate of progression/regression of tricuspid regurgitation by Doppler-echocardiography [ Time Frame: 3 & 6 Months ] [ Designated as safety issue: No ]
Change on RV dimensions and function assessed by Doppler echocardiography [ Time Frame: 3 & 6 months ] [ Designated as safety issue: No ]
Change on RV volumes and function assessed by cardiac magnetic resonance [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
Change on the right catheterization hemodynamic parameters [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
Identify patients who are more likely to respond to therapy by pharmacogenetics analysis [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

Estimated Enrollment:	354
Study Start Date:	April 2009
Estimated Study Completion Date:	October 2011
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sildenafil: Experimental	Drug: Sildenafil Citrate 40 mg t.i.d.
Placebo: Placebo Comparator	Drug: Placebo Placebo t.i.d.

Detailed Description:

Phase IV, prospective, multicenter, randomized, double-blind, placebo-controlled, academically funded clinical trial, with 6 months follow-up. A total of 354 patients will be recruited. Inclusion criteria are: 1) successful surgical or percutaneous repair of a cardiac valve at least one year before screening and 2) persistent moderate or severe PH, and 3) absence of any residual significant valvular lesion. Patients will be randomized 1:1 to received sildenafil 40 mg t.i.d. or placebo. The primary endpoint is a clinical composite score combining: all-cause mortality, hospital admission for heart failure, World Health Organization (WHO) functional class, and the patient global assessment score. Additional clinical and mechanistic secondary end-points are defined.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age at the date of selection ≥ 18 years
Mean pulmonary pressure ≥ 30 mmHg, measured by a Swan-Ganz catheter placed in the pulmonary artery
Heart valve intervention: surgical or percutaneous replacement, repair or dilatation performed at least one year before inclusion
Stable clinical condition for at least one month, without hospital admissions for heart failure, and on appropriate and stable doses of conventional cardiovascular medications

Exclusion Criteria:

Requiring or likely to require the following medications: organic nitrates, alpha-blocker therapy, potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, cimetidine, HIV protease inhibitors such ritonavir and saquinavir) Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
Patients with resting hypotension, with systolic blood pressure < 90 mmHg
Patients with retinitis pigmentosa
Anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia)
Severe renal impairment with creatinine clearance < 30 ml/min
Significant hepatic dysfunction
Prosthesis or valvular dysfunction with hemodynamic repercussion.
Pregnant or breast-feeding women
Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent
Life expectancy less than 2 years due to non-cardiac disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00862043

Contacts

Contact: Javier Bermejo, MD, PhD	34 91 5868815	jbermejot@gmail.com
Contact: Raquel Yotti, MD, PhD	34 91 5868279	ryotti@gmail.com

Locations

Spain
Hospital Vall d'Hebron	Not yet recruiting
Barcelona, Spain
Principal Investigator: Pilar Tornos, MD, PhD
Hospital Juan Canalejo	Recruiting
La Coruna, Spain
Sub-Investigator: Maria G Crespo, MD, PhD
Principal Investigator: Jose Cuenca, MD, PhD
Hospital de Leon	Recruiting
Leon, Spain
Principal Investigator: Mario Castano, MD
Sub-Investigator: Armando Perez de Prado, MD
Hospital General Universitario Gregorio Maranon	Recruiting
Madrid, Spain, 28007
Principal Investigator: Javier Bermejo, MD, PhD
Sub-Investigator: Raquel Yotti, MD, PhD
Hospital 12 de Octubre	Recruiting
Madrid, Spain
Principal Investigator: Carlos Saenz de la Calzada, MD, PhD
Sub-Investigator: Pilar Escribano, MD, PhD
Hospital Virgen de la Victoria	Recruiting
Malaga, Spain
Principal Investigator: Eduardo de Teresa, MD, PhD
Sub-Investigator: Manuel Jiménez-Navarro, MD, PhD
Hospital Universitario de Salamanca	Recruiting
Salamanca, Spain
Principal Investigator: Jose Maria Gonzalez-Santos, MD, PhD
Sub-Investigator: Candido Martin-Luengo, MD, PhD
Hospital Clínico de Valladolid	Recruiting
Valladolid, Spain
Principal Investigator: Jose A San-Roman, MD, PhD
Sub-Investigator: Luis de la Fuente, MD, PhD
Spain, Mallorca
Hospital Son Dureta	Recruiting
Palma de Mallorca, Mallorca, Spain
Principal Investigator: Armando Bethencourt, MD, PhD
Sub-Investigator: Alfredo Gómez-Jaume, MD

Sponsors and Collaborators

Hospital General Universitario Gregorio Marañon

Instituto de Salud Carlos III

Investigators

Principal Investigator:

Javier Bermejo, MD, PhD

Hospital General Universitario Gregorio Maranon

More Information

Additional Information:

Promoter Research Foundation This link exits the ClinicalTrials.gov site

Funding Agent This link exits the ClinicalTrials.gov site

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fundacion para la Investigacion Biomedica Hospital Gregorio Maranon ( Gerente )
Study ID Numbers:	FIBHGM-SIOVAC, EudraCT: 2007-007033-40, EC07-90772
Study First Received:	March 13, 2009
Last Updated:	June 29, 2009
ClinicalTrials.gov Identifier:	NCT00862043 History of Changes
Health Authority:	Spain: Spanish Agency of Medicines; Spain: Ministry of Health; Spain: Ethics Committee

Keywords provided by Hospital General Universitario Gregorio Marañon:

Secondary Pulmonary Hypertension
Valvular Heart Disease
Phosphodiesterase-Inhibitors
Sildenafil
Outcomes Research

Study placed in the following topic categories:

Vasodilator Agents
Heart Diseases
Citric Acid
Vascular Diseases
Sildenafil
Cardiovascular Agents
Secondary Pulmonary Hypertension
Heart Valve Diseases

Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Hypertension, Pulmonary
Lung Diseases
Neoplasm Metastasis
Citrate
Hypertension

Additional relevant MeSH terms:

Vasodilator Agents
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Vascular Diseases
Sildenafil
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions

Heart Valve Diseases
Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Hypertension, Pulmonary
Therapeutic Uses
Lung Diseases
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on September 11, 2009