Clinical trial NCT02742909: Acute Effects of rhBNP in Patients With PH Associated With Acute Exacerbation of Chronic Pulmonary Disease
Official title: Acute Effect of Recombinant Human Brain Natriuretic Peptide in Patients With Pulmonary Hypertension Associated With Acute Exacerbation of Chronic Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Hypertension
Lead sponsor: Shengjing Hospital
Sponsor class: OTHER
First posted: 2016-04-19
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: pulmonary artery systolic pressure (PASP) measured by Swan-Ganz catheter
timeFrame: baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours
measure: pulmonary artery diastolic pressure(PADP) measured by Swan-Ganz catheter
timeFrame: baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours
measure: mean pulmonary artery pressure(mPAP) measured by Swan-Ganz catheter
timeFrame: baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours
measure: pulmonary vascular resistance(PVR) measured by Swan-Ganz catheter
timeFrame: baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours
measure: cardiac output(CO) measured by Swan-Ganz catheter
timeFrame: baseline , 0.5 hour, 1hour, 2hours, 4hours, 8hours, 12hours, 20hours, 24hours, 27hours and 30hours
Secondary outcomes:
measure: heat rate (HR)
timeFrame: baseline and 30 hours
measure: respiratory rate(RR)
timeFrame: baseline and 30 hours
measure: blood pressure(BP)
timeFrame: baseline and 30 hours
measure: blood oxygen saturation(SPO2)
timeFrame: baseline and 30 hours
measure: Brog classification
timeFrame: baseline and 30 hours
measure: Brain Natriuretic Peptide(BNP) in blood
timeFrame: baseline and 30 hours
measure: N-terminal pro-Brain Natriuretic Peptide(NT-pro BNP) in blood
timeFrame: baseline and 30 hours
measure: Potential of Hydrogen(PH) in artery blood gas analysis
timeFrame: baseline and 30 hours
measure: arterial partial pressure of oxygen(PaO2)
timeFrame: baseline and 30 hours
measure: arterial partial pressure of carbon dioxide (PaCO2)
timeFrame: baseline and 30 hours
measure: oxygenation index in artery blood gas analysis
timeFrame: baseline and 30 hours
measure: alveolar-arterial oxygen difference in artery blood gas analysis
timeFrame: baseline and 30 hours
Other outcomes:
Locations:
city: Shenyang
country: China
facility: Shenjing Hospital
state: Liaoning
Study officials:
affiliation: SHENJING HOSPTIAL OF CHINA MEDICAL UNIVERSITY
name: LI ZHAO, DOCTOR
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Mingguang Huang,Yingjun Dong. Clinical observation on rhBNP in treating patients with pulmonary artery hypertension. Shanxi Medical Journal,2011,40(6):545-546.