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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: rhBNP; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shenjing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age>18 years old, male or female;
2. in acute exacerbation period and with a history of chronic respiratory diseases;
3. cardiac ultrasound showed a pulmonary hypertension ≥50mmHg;
4. grade II or WHO grade of heart function;
5. signed informed consent.

Exclusion Criteria:

1. pulmonary hypertension not associated with chronic lung disease;
2. Acute or severe chronic left heart failure;
3. severe respiratory failure during receipt of non-invasive or invasive ventilator therapy;
4. mPAP≤25mmHg or pulmonary capillary wedge pressure (PCWP) ≥15mmHg at rest as assessed by Swan- Ganz catheter;
5. a high risk of hypotension (systolic pressure <100 mmHg or 110 mmHg with the use of intravenous nitroglycerin);
6. Uncontrolled arterial hypertension;
7. acute coronary syndrome;
8. Severe left ventricular hypertrophy;
9. Congenital or acquired valvular or myocardial disease;
10. end-stage renal disease during receipt of renal replacement therapy;
11. clinically significant anemia;
12. other contraindications for vasodilators;
13. treatment with dobutamine (at a dose ≥5 μg per kilogram of body weight per minute);
14. treatment with milrinone or levosimendan within the previous 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rhBNP; 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; rhBNP was administered as a continuous infusion for 24 hours before or after placebo; Other Names: Recombinant Human Brain Natriuretic Peptide
Placebo Comparator: Placebo; 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; normal saline as a placebo was administered as a continuous infusion for 24 hours; Other Names: normal saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: LI ZHAO
• Investigators: Principal Investigator: LI ZHAO, DOCTOR, SHENJING HOSPTIAL OF CHINA MEDICAL UNIVERSITY

Publications and helpful links

General Publications

• Haeck ML, Vliegen HW. Diagnosis and treatment of pulmonary hypertension. Heart. 2015 Feb;101(4):311-9. doi: 10.1136/heartjnl-2011-301386. Epub 2014 May 22. No abstract available.
• O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalan R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Mendez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011 Jul 7;365(1):32-43. doi: 10.1056/NEJMoa1100171. Erratum In: N Engl J Med. 2011 Aug 25;365(8):773. Wilson, W H [corrected to Tang, W H W].
• Mingguang Huang,Yingjun Dong. Clinical observation on rhBNP in treating patients with pulmonary artery hypertension. Shanxi Medical Journal,2011,40(6):545-546.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: October 9, 2015
• First Submitted That Met QC Criteria: April 13, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 29, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: SJHX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes