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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by Maryknoll Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Pusan National University Hospital
Inje University
Yeungnam University
Information provided by:
Maryknoll Medical Center
ClinicalTrials.gov Identifier:
NCT01383083
First received: November 29, 2010
Last updated: June 27, 2011
Last verified: November 2010
  Purpose

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


Condition Phase
Pulmonary Arterial Hypertension
Phase 4

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
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.

Resource links provided by NLM:


Further study details as provided by Maryknoll Medical Center:

Primary Outcome Measures:
  • Pulmonary Vascular Resistance [ Time Frame: Change from Baseline in PVR at 24 weeks ] [ Designated as safety issue: No ]
    To identify hemodynamic benefit and safety of 24 weeks treatment with iloprost on patients with Eisenmenger's syndrom


Secondary Outcome Measures:
  • Assessment of quality of life [ Time Frame: Change from Baseline in QoL at 24 weeks ] [ Designated as safety issue: No ]
    To investigate the change of quality of life(SF-12) after 24 weeks treatment with iloprost

  • Exercise capacity [ Time Frame: Change from baseline in exercise capacity at 24 weeks ] [ Designated as safety issue: No ]
    To investigate the change of exercise capacity(6-minute walking test) after 24 weeks treatment with iloprost


Estimated Enrollment: 42
Study Start Date: November 2010
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
iloprost
In the adult patient group, iloprost acceptable target dose is 2.5 ug 4-6 times/day according to the patient's compliance. Because of the concern of safety and tolerability, during the first 4 weeks of treatment, patients receive 2.5 ug twice daily. After 4 weeks, this is increased to the target dose, if iloprost is well tolerated.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with PAH associated with congenital systemic-to-pulmonary shuntand treated with iloprost for pulmonary hypertension

: patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome are included

Criteria

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)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01383083

Sponsors and Collaborators
Maryknoll Medical Center
Pusan National University Hospital
Inje University
Yeungnam University
Investigators
Principal Investigator: Kyoung Im Cho, MD Maryknoll General Hospital
  More Information

No publications provided

Responsible Party: Kyoung Im Cho, Maryknoll Medical Center
ClinicalTrials.gov Identifier: NCT01383083     History of Changes
Other Study ID Numbers: EIGER2011
Study First Received: November 29, 2010
Last Updated: June 27, 2011
Health Authority: Korea: Institutional Review Board

Keywords provided by Maryknoll Medical Center:
Pulmonary arterial hypertension
Congenital heart disease
Eisenmenger physiology

Additional relevant MeSH terms:
Heart Defects, Congenital
Heart Diseases
Hypertension
Hypertension, Pulmonary
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Iloprost
Cardiovascular Agents
Hematologic Agents
Pharmacologic Actions
Platelet Aggregation Inhibitors
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014