Sildenafil for Secondary Pulmonary Hypertension Due to Valvular Disease

NCT ID: NCT00862043

Last Updated: 2016-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2016-07-31

Brief Summary

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.

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.

Conditions

Pulmonary Hypertension; Valvular Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sildenafil Citrate

Sildenafil Citrate 40 mg t.i.d. oral

Group Type: EXPERIMENTAL

Sildenafil Citrate

Intervention Type: DRUG

40 mg t.i.d.

Placebo

Sildenafil-matched oral placebo 40 mg t.i.d

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo t.i.d.

Interventions

Sildenafil Citrate

40 mg t.i.d.

Intervention Type: DRUG

Placebo

Placebo t.i.d.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Fundación de Investigación en Red en Enfermedades Cardiovasculares

OTHER

Sponsor Role: collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Bermejo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Maranon

Locations

Hospital Universitario Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Hospital Universitario Alava

Vitoria-Gasteiz, Alava, Spain

Hospital German Trias y Pujol

Badalona, Barcelona, Spain

Hospital de la Santa Creu y San Pau

Barcelona, Barcelon, Spain

Hospital Reina Sofía

Córdoba, Córdoba, Spain

Hospital Juan Canalejo

A Coruña, La Coruna, Spain

Hospital de Leon

León, Leon, Spain

Hospital Fundación de Alcorcón

Alcorcón, Madrid, Spain

Hospital General Universitario Gregorio Maranon

Madrid, Madrid, Spain

Hospital 12 de Octubre

Madrid, Madrid, Spain

Hospital Infanta Leonor

Madrid, Madrid, Spain

Hospital Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Virgen de la Victoria

Málaga, Malaga, Spain

Hospital Universitario de Salamanca

Salamanca, Salamanca, Spain

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Tenerife, Spain

Hospital Clínico de Valladolid

Valladolid, Valladolid, Spain

Hospital de Galdakao

Galdakao, Vizcaya, Spain

Hospital Virgen de las Nieves

Granada, , Spain

Countries

Spain

References

Bermejo J, Gonzalez-Mansilla A, Mombiela T, Fernandez AI, Martinez-Legazpi P, Yotti R, Garcia-Orta R, Sanchez-Fernandez PL, Castano M, Segovia-Cubero J, Escribano-Subias P, Alberto San Roman J, Borras X, Alonso-Gomez A, Botas J, Crespo-Leiro MG, Velasco S, Bayes-Genis A, Lopez A, Munoz-Aguilera R, Jimenez-Navarro M, Gonzalez-Juanatey JR, Evangelista A, Elizaga J, Martin-Moreiras J, Gonzalez-Santos JM, Moreno-Escobar E, Fernandez-Aviles F; SIOVAC ("Sildenafil for Improving Outcomes after VAlvular Correction") Investigators. Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival. J Am Heart Assoc. 2021 Jan 19;10(2):e019949. doi: 10.1161/JAHA.120.019949. Epub 2021 Jan 5.

Reference Type: DERIVED

PMID: 33399006 (View on PubMed)

Bermejo J, Yotti R, Garcia-Orta R, Sanchez-Fernandez PL, Castano M, Segovia-Cubero J, Escribano-Subias P, San Roman JA, Borras X, Alonso-Gomez A, Botas J, Crespo-Leiro MG, Velasco S, Bayes-Genis A, Lopez A, Munoz-Aguilera R, de Teresa E, Gonzalez-Juanatey JR, Evangelista A, Mombiela T, Gonzalez-Mansilla A, Elizaga J, Martin-Moreiras J, Gonzalez-Santos JM, Moreno-Escobar E, Fernandez-Aviles F; Sildenafil for Improving Outcomes after VAlvular Correction (SIOVAC) investigators. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J. 2018 Apr 14;39(15):1255-1264. doi: 10.1093/eurheartj/ehx700.

Reference Type: DERIVED

PMID: 29281101 (View on PubMed)

Related Links

http://www.mineco.gob.es

Funding Agent

http://www.redcardiovascular.com

Cardiovascular Research Spanish National Network

Other Identifiers

2007-007033-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EC07-90772

Identifier Type: OTHER

Identifier Source: secondary_id

FIBHGM-SIOVAC

Identifier Type: -

Identifier Source: org_study_id