Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial

J Thromb Haemost. 2014 Apr;12(4):459-68. doi: 10.1111/jth.12521.

Abstract

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.

Keywords: pulmonary embolism; quality of life; randomized controlled trial; thrombolytic therapy; ventricular function, right.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Dyspnea / complications
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / complications
  • Humans
  • Male
  • Middle Aged
  • Probability
  • Prospective Studies
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Quality of Life
  • Shock / complications
  • Tenecteplase
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator
  • Tenecteplase