title: Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial.
abstract: BACKGROUND
  Optimal dosing of the recombinant tissue-type plasminogen activator (rt-PA) is important in treating pulmonary thromboembolism (PTE). The aim of this study was to compare the efficacy and safety of a 50 mg/2 h rt-PA regimen with a 100 mg/2 h rt-PA regimen in patients with acute PTE.
  
  
  METHODS
  A prospective, randomized, multicenter trial was conducted in which 118 patients with acute PTE and either hemodynamic instability or massive pulmonary artery obstruction were randomly assigned to receive a treatment regiment of either rt-PA at 50 mg/2 h (n = 65) or 100 mg/2 h (n = 53). The efficacy was determined by observing the improvements of right ventricular dysfunctions (RVDs) on echocardiograms, lung perfusion defects on ventilation perfusion lung scans, and pulmonary artery obstructions on CT angiograms. The adverse events, including death, bleeding, and PTE recurrence, were also evaluated.
  
  
  RESULTS
  Progressive improvements in RVDs, lung perfusion defects, and pulmonary artery obstructions were found to be similarly significant in both treatment groups. This is true for patients with either hemodynamic instability or massive pulmonary artery obstruction. Three (6%) patients in the rt-PA 100 mg/2 h group and one (2%) in the rt-PA 50 mg/2 h group died as the result of either PTE or bleeding. Importantly, the 50 mg/2 h rt-PA regimen resulted in less bleeding tendency than the 100 mg/2 h regimen (3% vs 10%), especially in patients with a body weight < 65 kg (14.8% vs 41.2%, P = .049). No fatal recurrent PTE was found in either group.
  
  
  CONCLUSIONS
  Compared with the 100 mg/2 h regimen, the 50 mg/2 h rt-PA regimen exhibits similar efficacy and perhaps better safety in patients with acute PTE. These findings support the notion that optimizing rt-PA dosing is worthwhile when treating patients with PTE.
  
  
  BACKGROUND
  clinicaltrials.gov; Identifier: NCT00781378.
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhai
authors.forename: Yuanhua
authors.initials: Y
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Lirong
authors.initials: L
authors.lastname: Liang
authors.forename: Huaping
authors.initials: H
authors.lastname: Dai
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
authors.forename: Weixuan
authors.initials: W
authors.lastname: Lu
authors.forename: Zhonghe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiansheng
authors.initials: X
authors.lastname: Cheng
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000792:Angiography; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000008:administration & dosage*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000502:physiology; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator