rhBNP in Type 3 Pulmonary Hypertension

October 9, 2023 updated by: LI ZHAO, Shengjing Hospital

A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study on the Efficacy and Safety of Recombinant Human Brain Natriuretic Peptide in Improving Type 3 Pulmonary Hypertension.

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The study was divided into three stages, including screening period (3 days), treatment period (72 hours) and follow-up period (10 ± 2 days and 30 ± 5 days). Clinical visits were conducted for 5 times, including admission(screening - V0), V1 (randomization), the end of treatment (V2) and 10 ± 2 days before discharge (V3) in the research center; The telephone interview will be followed up and evaluated on the 30th ± 5 day (V4).

After the subjects signed the informed consent form, they completed all screening tests. The qualified subjects immediately started the basic treatment of Group 3 pulmonary hypertension. Three days later, they underwent right heart echocardiography and Swan-Ganz catheterization. The qualified subjects who met all the inclusion criteria and did not meet all the exclusion criteria were randomly allocated to the rhBNP treatment group or the placebo group at a ratio of 1:1, and the course of treatment was 72 hours. Due to the potential risk of hypotension, blood pressure should be monitored regularly during study drug administration. After the treatment, continue to follow up once by telephone, and the whole study period is 33 ± 5 days. During the whole treatment period, the study doctor recorded symptoms, vital signs, physical examination, and adverse reactions (AE/SAE) according to the requirements of the visit.

Except for emergency safety issues, no protocol violation or exemption is allowed. Therefore, the study must be carried out according to the study design, including the operation items specified in the time and event table.

Study Type

Interventional

Enrollment (Estimated)

72

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Guangdong Provincial Hospital of Traditional Chinese Medicine
    • Liaoning
      • Shenyang, Liaoning, China, 110004
        • Shengjing Hospital Of China Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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;
  2. At rest, the systolic pressure of pulmonary artery measured by right heart Doppler ultrasound was ≥ 50mmHg;
  3. At rest, the mean pulmonary artery pressure (mPAP) measured by Swan Ganz catheter was ≥ 25mmHg with PVR ≥ 3WU and PAWP < 15mmHg;
  4. Male or female, age ≥ 18 years old, weight ≥ 30kg ~ ≤ 150kg;
  5. WHO fc ≥ II.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: recombinant human brain natriuretic peptide
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
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.
Placebo Comparator: placebo
loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean pulmonary artery pressure (mPAP)
Time Frame: 72 hours
measured by Swan-Ganz catheter
72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systolic pressure of pulmonary artery（PASP）
Time Frame: Day 10±2
measured by Right heart echocardiography
Day 10±2
6MWD
Time Frame: Day 10±2
6-minute walk distance
Day 10±2
WHO fc
Time Frame: 72 hours
Score Sheet
72 hours
Oxygen partial pressure
Time Frame: 72 hours
Arterial blood gas analysis
72 hours
dyspnea
Time Frame: 72 hours
Score Sheet
72 hours
NT-proBNP
Time Frame: 72 hours
Blood
72 hours
acute event
Time Frame: Day 30±2
Symptoms, signs and laboratory examinations
Day 30±2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shengjing Hospital

Investigators

  • Principal Investigator: Li Zhao, Doctor, Shengjing Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2023

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

March 30, 2024

Study Registration Dates

First Submitted

September 14, 2022

First Submitted That Met QC Criteria

January 30, 2023

First Posted (Actual)

February 8, 2023

Study Record Updates

Last Update Posted (Actual)

October 10, 2023

Last Update Submitted That Met QC Criteria

October 9, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • rhBNP-PH2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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