Effects of Iloprost Treatment in Adult Patients With Pulmonary Arterial Hypertension Related to Congenital Heart Disease

Pulmonary Arterial Hypertension Clinical Trial

— EIGER  

Official title:

Effects of Iloprost Treatment in Adult Patients With Pulmonary Arterial Hypertension Related to Congenital Heart Disease (Eisenmenger Physiology): Safety, Tolerability, Clinical, and Hemodynamic Effect.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01383083
• Other study ID #: EIGER2011
• Status: Active, not recruiting
• Phase: Phase 4
• First received: November 29, 2010
• Last updated: June 27, 2011
• Start date: November 2010
• Est. completion date: November 2012

Study information

• Verified date: November 2010
• Source: Maryknoll Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25-50% of this population affected by Eisenmenger's syndrome. The rarity of this syndrome, combined with its complex pathophysiology, account for the insufficient understanding of the principles underlying its proper treatment.Recent decades have seen developments in pulmonary hypertension pathophysiology which have led to the introduction of new groups of drugs: prostacycline analogs (Epoprostenol, Treprostinil, Beraprost, Illoprost), phosphodiesterase inhibitors (Sildenafil, Tadalafil), endothelin receptor antagonists (Bosentan, Sitaxantan, Ambrisentan) and nitric oxide. These drugs should be administered to patients in III-IV NYHA class. Despite successful early results, the therapeutic effect on patients with Eisenmenger syndrome has not been conclusively established The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger's syndrome is based mainly on clinical experience rather than being evidence based. Although Eisenmenger's syndrome is uncurable disease, the survival rate is relatively higher than primary PAH, and the patients with Eisenmenger's syndrome are relatively younger group. So the improvement of exercise tolerance and quality of life is very important. Several randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger's syndrome. However, there was scare data of outcomes of treatment with the inhaled iloprost in patients with Eisenmenger's syndrome. In Korea, most of patients with Eisenmenger's syndrome are treated with conservative therapy instead of administration of PAH-specific drug, because of lack of clinical experience. Moreover, oral agent such as bosentan, sidenafil is preferred than iloprost becase of more evidence and convenience. Our therapeutic efforts should be directed mainly towards preventing complications. As a rule, we should avoid agents with no established therapeutic efficacy and try to alleviate symptoms without any additional risk, so as not to disrupt the existing clinical balance.

In this study, we investigate to know the clinical benefit of iloprost on patients with Eisenmenger's syndrome by the use of functional and hemodynamic parameters, which would add the evidence of PAH-specific agents on the Eisenmenger's syndrome

Description:

A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger's syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: November 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients with Eisenmenger syndrome are clinically stable and in World Health Organization functional class (WHO class) III or worse are selected for treatment.

2. Eisenmenger syndrome is diagnosed echocardiographically as right-to-left shunting through the shunt defect.

3. To exclude other causes of PAH, lung function tests (spirometry, forced expiratory volume in 1 second, and forced vital capacity)are obtained.

Exclusion Criteria:

1. Patients with severe left ventricular dysfunction and/or pulmonary venous congestion (measured invasively or assessed echocardiographically) are excluded.

2. Patients with obstruction of the right ventricular outflow tract, pulmonary valve, or pulmonary arteries or patients on prostacyclin, glibenclamide, or cyclosporine treatment were excluded.

3. Patients with contraindication to Ventavis;

• Hypersensitive to Ventavis

• High risk of bleeding, which can be increased by use of Ventavis (e.g. active peptic ulcer, trauma, intracranial hemorrhage)

• Severe coronary disease, unstable angina, history of Acute myocardial infarction within 6 months, uncompensated heart failure not under close medical monitoring, severe arrhythmia, suspected pulmonary congestion, cerebrovascular disease within 3 months (e.g. transient ischemic attack, stoke)

• pulmonary hypertension due to venous occlusive disease

• valvular defect with dysfunction of cardiac muscle, which is independent of pulmonary hypertension

• pregnancy, women with high probability of pregnancy, breast feeding

• renal failure (creatinine clearance <30mL/min)

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Heart Defects, Congenital
• Heart Diseases
• Hypertension
• Pulmonary Arterial Hypertension

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Maryknoll Medical Center	Inje University, Pusan National University Hospital, Yeungnam University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Vascular Resistance	To identify hemodynamic benefit and safety of 24 weeks treatment with iloprost on patients with Eisenmenger's syndrom	Change from Baseline in PVR at 24 weeks	No
Secondary	Assessment of quality of life	To investigate the change of quality of life(SF-12) after 24 weeks treatment with iloprost	Change from Baseline in QoL at 24 weeks	No
Secondary	Exercise capacity	To investigate the change of exercise capacity(6-minute walking test) after 24 weeks treatment with iloprost	Change from baseline in exercise capacity at 24 weeks	No