Group 3 Pulmonary Hypertension Clinical Trial
Official title:
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.
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. ;