Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial

Chen Wang, Zhenguo Zhai, Yuanhua Yang, Qi Wu, Zhaozhong Cheng, Lirong Liang, Huaping Dai, Kewu Huang, Weixuan Lu, Zhonghe Zhang, Xiansheng Cheng, Ying H Shen, China Venous Thromboembolism (VTE) Study Group, Chen Wang, Xiansheng Cheng, Xinzhi Weng, Weixuan Lu, Quanying He, Yiming Zhao, Binrong Ma, Nanshan Zhong, Xiansheng Cheng, Ruping Dai, Youmin Guo, Tie Wang, Weixuan Lu, Quanying He, Yiming Zhao, Chen Wang, Yuanhua Yang, Zhenguo Zhai, Lirong Liang, Chen Wang, Yuanhua Yang, Zhenguo Zhai, Baosen Pang, Yafeng Wu, Xiaojuan Wang, Tie Zhaohui Tong, Qi Wu, Yanling Yin, Wei Zhou, Zhaozhong Cheng, Handong Jiang, Shaoxian Chen, Yupeng Xie, Zhuang Ma, Ping Chen, Lei Liu, Jin Zhang, Xiwei Zheng, Shengwen Chen, Chen Qiu, Yongcheng Du, Jianying Xu, Xiaoyun Hu, Yadong Yuan, Baofa Wang, Jian Kang, Lili Tian, Zhengyi He, Yongchang Sun, Wanzhen Yao, Yuxiang Liu, Zhuola Liu, Xu Wang, Weixuan Lu, Chunping Liu, Yongjian Liu, Nanshan Zhong, Rongchang Chen, Hua Wu, Tiantuo Zhang, Kejing Ying, Liying Chen, Ming Bai, Guangfa Wang, Chunhua Chi, Shi Wang, Shuyue Xia, Quanying He, Xingyu Tan, Huilin Liu, Yingqi Zhang, Canmao Xie, Mian Zeng, Yiqiang Chen, Shenglan Guo, Tangwei Liu, Peizong Sun, Jie Chen, Xinrong Liu, Hongyang Wang, Yunyou Duan, Zhoushan Nie, Xiaoping Xiang, Chun Zhang, Baomin Fang, Tieying Sun, Chen Wang, Zhenguo Zhai, Yuanhua Yang, Qi Wu, Zhaozhong Cheng, Lirong Liang, Huaping Dai, Kewu Huang, Weixuan Lu, Zhonghe Zhang, Xiansheng Cheng, Ying H Shen, China Venous Thromboembolism (VTE) Study Group, Chen Wang, Xiansheng Cheng, Xinzhi Weng, Weixuan Lu, Quanying He, Yiming Zhao, Binrong Ma, Nanshan Zhong, Xiansheng Cheng, Ruping Dai, Youmin Guo, Tie Wang, Weixuan Lu, Quanying He, Yiming Zhao, Chen Wang, Yuanhua Yang, Zhenguo Zhai, Lirong Liang, Chen Wang, Yuanhua Yang, Zhenguo Zhai, Baosen Pang, Yafeng Wu, Xiaojuan Wang, Tie Zhaohui Tong, Qi Wu, Yanling Yin, Wei Zhou, Zhaozhong Cheng, Handong Jiang, Shaoxian Chen, Yupeng Xie, Zhuang Ma, Ping Chen, Lei Liu, Jin Zhang, Xiwei Zheng, Shengwen Chen, Chen Qiu, Yongcheng Du, Jianying Xu, Xiaoyun Hu, Yadong Yuan, Baofa Wang, Jian Kang, Lili Tian, Zhengyi He, Yongchang Sun, Wanzhen Yao, Yuxiang Liu, Zhuola Liu, Xu Wang, Weixuan Lu, Chunping Liu, Yongjian Liu, Nanshan Zhong, Rongchang Chen, Hua Wu, Tiantuo Zhang, Kejing Ying, Liying Chen, Ming Bai, Guangfa Wang, Chunhua Chi, Shi Wang, Shuyue Xia, Quanying He, Xingyu Tan, Huilin Liu, Yingqi Zhang, Canmao Xie, Mian Zeng, Yiqiang Chen, Shenglan Guo, Tangwei Liu, Peizong Sun, Jie Chen, Xinrong Liu, Hongyang Wang, Yunyou Duan, Zhoushan Nie, Xiaoping Xiang, Chun Zhang, Baomin Fang, Tieying Sun

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.

Trial registration: clinicaltrials.gov; Identifier: NCT00781378.

Figures

Figure 1
Figure 1
Flow study diagram. rt-PA = recombinant tissue-type plasminogen activator.
Figure 2
Figure 2
Comparison of the right side of the heart functions (A), lung perfusion defect scores (B), and pulmonary artery obstruction scores (C) between the two treatments for PTE. PTE = pulmonary thromboembolism; RVED/LVED = right and left ventricular end-diastolic diameter ratio in the parasternal long-axis view; RVWM = right ventricular wall movements; SPAP = systolic pulmonary artery pressure. See Figure 1 legend for expansion of other abbreviations.
Figure 3
Figure 3
Comparisons of total bleeding complications between two treatments for PTE in patients with different body weights and BMI subgroups. See Figure 1, Figure 2 legends for expansion of other abbreviations.

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