Acute Effects of rhBNP in Patients With PH Associated With Acute Exacerbation of Chronic Pulmonary Disease

Study Overview
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Brief Summary
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To evaluate the acute effect of recombinant human brain natriuretic peptide(rhBNP) on pulmonary hypertension of acute exacerbations of chronic pulmonary disease. rhBNP was administered as a continuous infusion for 24 hours , pulmonary artery pressure and other hemodynamic parameters were monitored by Swan- Ganz catheter.

Detailed Description
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Pulmonary hypertension (PH) is a descriptive name for abnormally elevated pressures in the pulmonary vasculature, which seriously affects the quality of life and survival of patients. Currently, no effective drugs treatment was used in patients with pulmonary hypertension due to acute exacerbation of lung disease. Recombinant Human Brain Natriuretic Peptide (rhBNP)was approved in 2001 for use in patients with acute heart failure on the basis of studies showing a reduction in pulmonary-capillary wedge pressure(PCWP) and pulmonary arterial pressure (PAP) and improvement cardiac output (CO) . Thus, the study was designed to administer rhBNP as a continuous infusion for 24 hours on pulmonary hypertension of acute exacerbations of chronic pulmonary disease monitoring by Swan- Ganz catheter. Each patient was studied on two occasions (6 hours apart). One occasion the subject received rhBNP 1.5ug/kg IV bolus followed by an infusion of 0.0075ug/kg/min for 24 hours; other occasion the subject received IV placebo bolus followed by a placebo infusion for 24 hours .these were administered in random order in double blind fashion.

Official Title
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Acute Effect of Recombinant Human Brain Natriuretic Peptide in Patients With Pulmonary Hypertension Associated With Acute Exacerbation of Chronic Pulmonary Disease

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: rhBNP
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age>18 years old, male or female; in acute exacerbation period and with a history of chronic respiratory diseases; cardiac ultrasound showed a pulmonary hypertension ≥50mmHg; grade II or WHO grade of heart function; signed informed consent. Exclusion Criteria: pulmonary hypertension not associated with chronic lung disease; Acute or severe chronic left heart failure; severe respiratory failure during receipt of non-invasive or invasive ventilator therapy; mPAP≤25mmHg or pulmonary capillary wedge pressure (PCWP) ≥15mmHg at rest as assessed by Swan- Ganz catheter; a high risk of hypotension (systolic pressure <100 mmHg or 110 mmHg with the use of intravenous nitroglycerin); Uncontrolled arterial hypertension; acute coronary syndrome; Severe left ventricular hypertrophy; Congenital or acquired valvular or myocardial disease; end-stage renal disease during receipt of renal replacement therapy; clinically significant anemia; other contraindications for vasodilators; treatment with dobutamine (at a dose ≥5 μg per kilogram of body weight per minute); treatment with milrinone or levosimendan within the previous 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rhBNP<br>the study is a self controlled study. Each patient was studied on two occasions (6 hours apart). One occasion the subject received rhBNP 1.5ug/kg IV bolus followed by an infusion of 0.0075ug/kg/min for 24 hours; other occasion the subject received IV placebo bolus followed by a placebo infusion for 24 hours .these were administered in random order in double blind fashion.The date of this arm is from the occasion the subject received rhBNP. | Drug: rhBNP<br>* rhBNP was administered as a continuous infusion for 24 hours before or after placebo<br>* Other names: Recombinant Human Brain Natriuretic Peptide;|
| Placebo Comparator: Placebo<br>the study is a self controlled study. Each patient was studied on two occasions (6 hours apart). One occasion the subject received rhBNP 1.5ug/kg IV bolus followed by an infusion of 0.0075ug/kg/min for 24 hours; other occasion the subject received IV placebo bolus followed by a placebo infusion for 24 hours .these were administered in random order in double blind fashion.The date of this arm is from the occasion the subject received placebo. | Drug: placebo<br>* normal saline as a placebo was administered as a continuous infusion for 24 hours<br>* Other names: normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary artery systolic pressure (PASP) measured by Swan-Ganz catheter | we are going to record a change | baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours | 
| pulmonary artery diastolic pressure(PADP) measured by Swan-Ganz catheter | we are going to record a change | baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours | 
| mean pulmonary artery pressure(mPAP) measured by Swan-Ganz catheter | we are going to record a change | baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours | 
| pulmonary vascular resistance(PVR) measured by Swan-Ganz catheter | we are going to record a change | baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours | 
| cardiac output(CO) measured by Swan-Ganz catheter | we are going to record a change | baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| heat rate (HR) |  | baseline and 30 hours | 
| respiratory rate(RR) |  | baseline and 30 hours | 
| blood pressure(BP) |  | baseline and 30 hours | 
| blood oxygen saturation(SPO2) |  | baseline and 30 hours | 
| Brog classification | this is a classification table for patient' s feeling of fatigue and dyspnea. from 1 to 10 degree. | baseline and 30 hours | 
| Brain Natriuretic Peptide(BNP) in blood |  | baseline and 30 hours | 
| N-terminal pro-Brain Natriuretic Peptide(NT-pro BNP) in blood |  | baseline and 30 hours | 
| Potential of Hydrogen(PH) in artery blood gas analysis |  | baseline and 30 hours | 
| arterial partial pressure of oxygen(PaO2) |  | baseline and 30 hours | 
| arterial partial pressure of carbon dioxide (PaCO2) |  | baseline and 30 hours | 
| oxygenation index in artery blood gas analysis |  | baseline and 30 hours | 
| alveolar-arterial oxygen difference in artery blood gas analysis |  | baseline and 30 hours |