Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial.
BACKGROUND
Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance.


OBJECTIVE
Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE.


METHODS
Normotensive patients with PE and right ventricular (RV) strain (by echocardiography or biomarkers) were enrolled from eight hospitals. All patients received low-molecular-weight heparin followed by random assignment to either a single weight-based bolus of tenecteplase or placebo, administered in a double-blinded fashion. The primary composite outcome included: (i) death, circulatory shock, intubation or major bleeding within 5 days or (ii) recurrent PE, poor functional capacity (RV dysfunction with either dyspnea at rest or exercise intolerance) or an SF36(®) Physical Component Summary (PCS) score < 30 at 90-day follow-up.


RESULTS
Eighty-three patients were randomized; 40 to tenecteplase and 43 to placebo. The trial was terminated prematurely. Within 5 days, adverse outcomes occurred in three placebo-treated patients (death in one and intubation in two) and one tenecteplase-treated patient (fatal intracranial hemorrhage). At 90 days, adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus, 16 (37%) placebo-treated and six (15%) tenecteplase-treated patients had at least one adverse outcome (exact two-sided P = 0.017).


CONCLUSIONS
Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome.
Departments of Emergency Medicine and Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
J A
JA
Kline
K E
KE
Nordenholz
D M
DM
Courtney
C
C
Kabrhel
A E
AE
Jones
M T
MT
Rondina
D B
DB
Diercks
J R
JR
Klinger
J
J
Hernandez
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004417:Dyspnea / Q000150:complications; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D012769:Shock / Q000150:complications; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
pulmonary embolism; quality of life; randomized controlled trial; thrombolytic therapy; ventricular function, right