rhBNP in Type 3 Pulmonary Hypertension

NCT05716984 | Unknown Phase 4 DMC

• 1 other identifier: rhBNP-PH2022
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

Pulmonary hypertension is a common clinical syndrome, which seriously affects the quality of life and survival of patients. Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) to ≥20 mmHg at rest as measured invasively by right heart catheterisation (RHC). Pulmonary hypertension can be divided into five types, among which pulmonary hypertension caused by chronic pulmonary diseases and/or hypoxia is called Group 3 pulmonary hypertension, which is the most important factor of pulmonary heart disease. The drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in Group 3 PH, except indirect treatment methods such as improving hypoxia and controlling infection. Recombinant human brain natriuretic peptide (rhBNP) is a biological agent with a molecular weight of 3664Da synthesized by DNA technology. It is availble in China. It has many functions such as diuresis, vasodilation, inhibition of renin-angiotensin-aldosterone and sympathetic nervous systems, etc. RhBNP has been suggested in patients with acute myocardial infarction and congestive heart failure. In view of the dilating effect of rhBNP on pulmonary vessels, it is speculated that rhBNP may reduce type 3 pulmonary hypertension. Based on this hypothesis, we conducted a preliminary clinical trial. The results showed that, compared with the placebo group, after rhBNP was continuously pumped for 24 hours, the pulmonary artery hemodynamic indexes continuously monitored by Swan-Ganz catheter were significantly improved. In view of the pharmacological effect of rhBNP and our previous clinical trial results, this study intends to conduct a prospective, multicenter, placebo-controlled, double-blind clinical trial to evaluate the efficacy and safety of rhBNP in the treatment of patients with group 3 pulmonary hypertension.

Conditions

Group 3 Pulmonary Hypertension

Keywords

rhBNP; Group 3 Pulmonary Hypertension; Right cardiac catheter

Outcome Measures

Primary Outcomes (1)

• Mean pulmonary artery pressure (mPAP)

  measured by Swan-Ganz catheter

  72 hours

Secondary Outcomes (7)

• Systolic pressure of pulmonary artery（PASP）

  Day 10±2

• 6MWD

  Day 10±2

• WHO fc

  72 hours

• Oxygen partial pressure

  72 hours

• dyspnea

  72 hours

Study Arms (2)

recombinant human brain natriuretic peptide

ACTIVE COMPARATOR

loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.

Drug: recombinant human brain natriuretic peptide

placebo

PLACEBO COMPARATOR

loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.

Drug: Placebo

Interventions

recombinant human brain natriuretic peptide DRUG

rhBNP 500μg + 0.9% sodium chloride 50ml, the concentration is 10 μg/ml, loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.

recombinant human brain natriuretic peptide

Placebo DRUG

placebo 500μg + 0.9% sodium chloride 50ml, the concentration is 10 μg/ml, loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized patients with acute exacerbation of chronic lung diseases, including: chronic obstructive pulmonary disease, bronchiectasis, obsolete pulmonary tuberculosis, obstructive sleep apnea hypopnea syndrome and thoracic or spinal deformity;
• At rest, the systolic pressure of pulmonary artery measured by right heart Doppler ultrasound was ≥ 50mmHg;
• At rest, the mean pulmonary artery pressure (mPAP) measured by Swan Ganz catheter was ≥ 25mmHg with PVR ≥ 3WU and PAWP \< 15mmHg;
• Male or female, age ≥ 18 years old, weight ≥ 30kg \~ ≤ 150kg;
• WHO fc ≥ II.

You may not qualify if:

• Any other types of pulmonary hypertension;
• Other active respiratory diseases (such as active pulmonary tuberculosis, pulmonary fibrosis, etc.);
• Patients requiring invasive mechanical ventilation;
• At rest, PAWP measured by Swan Ganz catheter was ≥ 15mmhg;
• Uncontrolled hypertension;
• Systolic blood pressure \< 90mmHg;
• Dopamine dose ≥ 5 μ g•kg-1•min-1；
• At rest, Doppler echocardiography confirmed left ventricular outflow tract obstruction or left ventricular systolic dysfunction (EF ≤ 55%);
• Acute coronary syndrome;
• Severe renal insufficiency (GFR \< 30ml / min / 1.73m2);
• Significant anemia;
• Milrinone or levosimendan was used within 30 days before screening;
• Allergic to any component of rhBNP;
• Participated in other clinical trials within 30 days before screening;
• Unable to complete the visit task.

Sponsors & Collaborators

• Shengjing Hospital: lead

Study Sites (2)

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangzhou, Guangdong, China

Location

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

Location

Related Publications (6)

• Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A, Oudiz R, Satoh T, Torres F, Torbicki A. Diagnosis of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801904. doi: 10.1183/13993003.01904-2018. Print 2019 Jan.

  PMID: 30545972 BACKGROUND

• Ahmad K, Khangoora V, Nathan SD. Lung Disease-Related Pulmonary Hypertension. Cardiol Clin. 2022 Feb;40(1):77-88. doi: 10.1016/j.ccl.2021.08.005.

  PMID: 34809919 BACKGROUND

• Karnati S, Seimetz M, Kleefeldt F, Sonawane A, Madhusudhan T, Bachhuka A, Kosanovic D, Weissmann N, Kruger K, Ergun S. Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target. Front Cardiovasc Med. 2021 Apr 12;8:649512. doi: 10.3389/fcvm.2021.649512. eCollection 2021.

  PMID: 33912600 BACKGROUND

• Pan HY, Zhu JH, Gu Y, Yu XH, Pan M, Niu HY. Comparative effects of recombinant human brain natriuretic peptide and dobutamine on acute decompensated heart failure patients with different blood BNP levels. BMC Cardiovasc Disord. 2014 Mar 4;14:31. doi: 10.1186/1471-2261-14-31.

  PMID: 24593826 BACKGROUND

• D'Alto M, Di Marco GM, D'Andrea A, Argiento P, Romeo E, Ferrara F, Lamia B, Ghio S, Rudski LG. Invasive and Noninvasive Evaluation for the Diagnosis of Pulmonary Hypertension: How to Use and How to Combine Them. Heart Fail Clin. 2018 Jul;14(3):353-360. doi: 10.1016/j.hfc.2018.02.010.

  PMID: 29966633 BACKGROUND

• Parikh KS, Rajagopal S, Arges K, Ahmad T, Sivak J, Kaul P, Shah SH, Tapson V, Velazquez EJ, Douglas PS, Samad Z. Use of outcome measures in pulmonary hypertension clinical trials. Am Heart J. 2015 Sep;170(3):419-29.e3. doi: 10.1016/j.ahj.2015.06.010. Epub 2015 Jun 19.

  PMID: 26385024 BACKGROUND

Study Officials

• Li Zhao, Doctor

  Shengjing Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: February 8, 2023
• Study Start: April 15, 2023
• Primary Completion: December 31, 2023
• Study Completion: March 30, 2024
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)