Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial.
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.
Wang
Chen
C
Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, Republic of China.
Zhai
Zhenguo
Z
Yang
Yuanhua
Y
Wu
Qi
Q
Cheng
Zhaozhong
Z
Liang
Lirong
L
Dai
Huaping
H
Huang
Kewu
K
Lu
Weixuan
W
Zhang
Zhonghe
Z
Cheng
Xiansheng
X
Shen
Ying H
YH
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
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator