Jeffrey A Kline, MD, Vice Chair of Research, Professor; Jackeline Hernandez, MD, Program Manager; Melanie M Hogg, BS, Program Manager; Alan E Jones, MD, Chair, Professor; D Mark Courtney, MD, Director of Research, Associate Professor; Christopher Kabrhel, MD, Director; Kristen E Nordenholz, MD, Associate Professor; Deborah B Diercks, MD, Vice Chair, Professor; Matthew T Rondina, MD, Associate Director, Associate Professor; James R Klinger, MD, Medical Director, Associate Professor.
Rationale and methodology for a multicentre randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes
Article first published online: 13 NOV 2013
© 2013 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Emergency Medicine Australasia
Volume 25, Issue 6, pages 515–526, December 2013
How to Cite
Kline, J. A., Hernandez, J., Hogg, M. M., Jones, A. E., Courtney, D. M., Kabrhel, C., Nordenholz, K. E., Diercks, D. B., Rondina, M. T. and Klinger, J. R. (2013), Rationale and methodology for a multicentre randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes. Emergency Medicine Australasia, 25: 515–526. doi: 10.1111/1742-6723.12159
Trial registration: NCT00680628.
- Issue published online: 5 DEC 2013
- Article first published online: 13 NOV 2013
- Genentech, Inc
- controlled trial;
- venous thromboembolism
Submassive pulmonary embolism (PE) has a low mortality rate but can degrade functional capacity.
The present study aims to provide rationale, methodology, and initial findings of a multicentre, randomised trial of fibrinolysis for PE that used a composite end-point, including quality of life measures.
This investigator-initiated study was funded by a contract between a corporate partner and the investigator's hospital (the prime site). The investigator was the Food and Drug Administration (FDA) sponsor. The prime site subcontracted, indemnified, and trained consortia members. Consenting, normotensive patients with PE and right ventricular strain (by echocardiography or biomarkers) received low-molecular-weight heparin and random assignment to a single bolus of tenecteplase or placebo in double-blinded fashion. The outcomes were: (i) in-hospital rate of intubation, vasopressor support, and major haemorrhage, or (ii) at 90 days, death, recurrent PE, or composite that defined poor quality of life (echocardiography, 6 min walk test and surveys). The planned sample size was n = 200.
Eight sites enrolled 87 patients over 5 years. The ratio of patients screened for each enrolled was 7.4 to 1, equating to 11 h screening time per patient enrolled. Primary barrier to enrolment was the cost of screening. Two patients died (2.5%, 95%CI [0–8%]), one developed shock, but 18 (22%, 95%CI: [13–30%]) had a poor quality of life.
An investigator-initiated, FDA-regulated, multicentre trial of fibrinolysis for submassive PE was conducted, but was limited by screening costs and a low mortality rate. Quality of life measurements might represent a more important patient-centred end-point.