Rationale and methodology for a multicentre randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes.
BACKGROUND
Submassive pulmonary embolism (PE) has a low mortality rate but can degrade functional capacity.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jeffrey A
JA
Kline
Jackeline
J
Hernandez
Melanie M
MM
Hogg
Alan E
AE
Jones
D Mark
DM
Courtney
Christopher
C
Kabrhel
Kristen E
KE
Nordenholz
Deborah B
DB
Diercks
Matthew T
MT
Rondina
James R
JR
Klinger
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011788:Quality of Life; D012107:Research Design; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
controlled trial; fibrinolysis; indemnification; methodology; thrombolysis; venous thromboembolism