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.
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Mean pulmonary artery pressure (mPAP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: recombinant human brain natriuretic peptide (Drug)
placebo
loading dose 1.5 μg/kg iv, followed by 0.0075 μg/kg·min with micro-pump injection for 72 hours.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean pulmonary artery pressure (mPAP)
时间窗: 72 hours
measured by Swan-Ganz catheter
次要结局
- 6MWD(Day 10±2)
- Oxygen partial pressure(72 hours)
- dyspnea(72 hours)
- NT-proBNP(72 hours)
- Systolic pressure of pulmonary artery（PASP）(Day 10±2)
- WHO fc(72 hours)
- acute event(Day 30±2)