- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01116063
Inhaled Iloprost for Disproportionate Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease (COPD) (COPDVEN)
Inhaled Iloprost for Disproportionate Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Pulmonary hypertension is frequently present in COPD and it is generally limited to a mild increase in mean pulmonary artery pressure. However some COPD patients are characterized by higher levels of mPAP at rest, fulfilling the definition of moderate or severe PH disproportionate PH .
In these patients the elevated pulmonary pressures adversely affect the prognosis.At the present time the evidence for the the use of specific pulmonary vasodilators in the management of these patients are scarce and cannot be recommended.the aim of this study is to evaluate the medium term efficacy and safety of the inhaled prostacyclin stable analog, iloprost in patients with COPD and moderate to severe pulmonary hypertension
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
While pulmonary hypertension is frequently present in COPD, particularly in the presence of hypoxemia, it is generally limited to a mild increase in mean pulmonary artery pressure in the face of a normal cardiac output.
Apart from this classical and widely observed profile of PH with modestly elevated mPAP, some COPD patients are characterized by higher levels of mPAP at rest, fulfilling the definition of moderate or severe PH . This kind of PH may be observed in patients presenting with a severe obstructive disease, but sometimes contrasts with a mild or moderate obstruction. In the latter case, the term disproportionate PH has been proposed, but it can be extended to describe all COPD patients with moderate to- severe PH.
Therefore, it is possible that in some patients with COPD, pulmonary hypertension contributes to the clinical picture because of right ventricular output limitation and is responsible for the poor prognosis of these patients, which is similar to that in primary pulmonary arterial hypertension.
The exact incidence of clinically significant pulmonary hypertension, defined as pulmonary hypertension that contributes to symptomatology and prognosis, is difficult to estimate in COPD. A prevalence of 5.8%- 13.5% in patients seems reasonable which would suggest an incidence of 1-3/10,000, which is 100 times the incidence of idiopathic pulmonary arterial hypertension.
These patients are characterized by marked effort dyspnea , profound hypoxemia, hypocapnia, moderate airway obstruction and a very low DLCO.
PH in COPD was an independent prognostic factor. Indeed, patients with similar airflow limitation had lower life expectancy when PH was resent. Patients with PH had a significantly lower survival rate at 5 yrs compared with patients without PH (33 versus 66%). Pathologic studies that stemmed from long-term oxygen trials pointed to the fact that pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD) is more than just medial hypertrophy from long-lasting hypoxic vasoconstriction. In these patients, all vessel wall layers appear to be involved, with intimal changes actually being the most prominent. Major remodeling of all pulmonary arterial vessel layers explains why pulmonary hypertension in COPD is often not,or minimally, reversible by supplemental oxygen, acutely or chronically. The pathobiology of pulmonary artery remodeling in advanced COPD remains incompletely explored. There are data supporting an endothelium-derived vasoconstrictor-dilator imbalance, mainly from a decreased endothelial nitric oxide expression. Plasma levels of ET-1 are increased both in patients with severe COPD and there is evidence that ETA and ETB receptor expression is increased in the pulmonary arteries of patients with COPD.
The major unmet medical need is the absence of a simple drug therapy that relieves the breathlessness or muscle fatigue, reduces pulmonary vascular resistance and the overloaded right ventricles that severely limits exercise tolerance in COPD and affects survival.
The only validated therapeutic approach of the 'common' PH in COPD patients is long-term oxygen therapy. A large variety of vasodilators has been tested in numerous studies both after short- and medium-term administration. The early enthusiasm vanished subsequently for several reasons: modesty of the vasodilator effect, inability for some drugs to sustain the acute benefit, no specificity of the vasodilator effect with concomitant systemic vasodilatation, deleterious effect on gas exchange due to a diminution of the ventilation/perfusion ratio and no demonstration of a survival benefit. At the present time vasodilators cannot be recommended in the management of COPD.
Treatments of PAH have shown a dramatic change in the past few years. Synthetic prostacyclin (epoprostenol), prostacyclin analogues, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors are in use in group I PAH with improve clinical outcome.
Based on analogy to primary pulmonary hypertension, a specific interventions aiming at the restoration of endothelial vasoconstrictor- dilator imbalance could be undertaken.
Selective pulmonary vasodilatation by inhalation of the vasorelaxant agent is an appealing concept to circumvent some of the hazards inherent in systemic vasodilator therapy in COPD patients with PH. Treatment of these patients with aerosolization of iloprost may reduce pulmonary vascular resistance , increases cardiac output while conserving ventilation-perfusion matching and and shunt preventing worsening of arterial hypoxia and wasting of the small ventilatory reserve of these patients.
In order to resolve these uncertainties we suggest evaluating the effectiveness of an inhaled iloprost in COPD patients with moderate to severe pulmonary hypertension. This evaluation would include monitoring and measurement of all the relevant cardio-respiratory variables as set out in detail below.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Yochai Adir, MD
- Phone Number: 972-4-8250517
- Email: YOCHAIAD@CLALIT.ORG.IL
Study Locations
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-
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Haifa, Israel
- Pulmoanry Division, Carmel Medical Center
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Contact:
- Yochai Adir, MD
- Phone Number: 972-4-8250517
- Email: YOCHAIAD@CLALIT.ORG.IL
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Principal Investigator:
- Yochai Adir, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient with COPD and increased SPAP >55 on echocardiogram will be screened for the study.
- Patients with normal wedge pressure ( [PCWP] ≤ 15 mm Hg), mean PAP ≥ 35 mm Hg and a pulmonary vascular resistance (PVR- 3.0 wood unit)on right heart catheterization.
- Diagnosis of COPD according to GOLD guidelines
- The patient can read, understand and sign the informed consent.
Exclusion Criteria:
1. Other identified cause for pulmonary hypertension
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single arm open label
All patients will receive the study drugs and will be evaluated
|
Inhalation Initial: 2.5 mcg/dose; if tolerated, increase to 5 mcg/dose; administer 6 times daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Pulmonary vascular resistance
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
6 minutes walking test
Time Frame: 6 months
|
6 months
|
Borg dyspnea score
Time Frame: 6 months
|
6 months
|
NT-BNP
Time Frame: 6 months
|
6 months
|
Arterial blood gases
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Yochai Adir, MD, Pulmoanry Division, Carmel Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- COPDVEN 2009
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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