Table 2.
Major randomized controlled trials for the treatment of intermediate-risk pulmonary embolism
| Study | Definition of intermediate-risk PE | Number of patients | Interventiona | Controla | Age, Mean (range or SD), y | Follow-up, d | Male, N° (%) | Primary outcome | Effect | Comment |
|---|---|---|---|---|---|---|---|---|---|---|
| Meyer et al (13), 2014 | RV dysfunction (by echo or CT) and elevated cTnI or T | 1005 | Tenecteplase (30–50 mg) |
Placebo | 66.2 (15.3) | 30 | 473 (47%) | All-cause mortality or hemodynamic collapse within 7 days after randomization | OR 0.44 (95% CI, 0.23–0.87; P =0.02) in favor of tenecteplase | No change in mortality; significant increase in bleeding |
| Kline et al (12), 2014 | Echocardiographic RV dysfunction, or elevated cTnI or T, or elevated BNP or NT-proBNP | 83 | Tenecteplase | Placebo | 55.4 (14) | 5 | 49 (59.0) | Composite of (1) death, circulatory shock requiring vasopressor support, need for intubation, or serious treatment-related adverse bleeding outcomes within 5 days posttreatment; and (2) VTE recurrence, poor functional capacity, or poor physical health-related quality of life within 90 days. | 37% placebo-treated and 15% tenecteplase-treated patients had at least one adverse outcome (P =0.02) | The trial was terminated prematurely |
| Sharifi et al (16), 2012 | Moderate PE (defined by radiologic thrombus burden) and ≥2 of the following: chest pain, tachypnea, tachycardia, dyspnea, cough, oxygen desaturation, or elevated jugular venous pressure | 121 | t-PA (50 mg) |
Placebo | Intervention: 58 (9) Control: 59 (10) |
840 | 55 (45.5) | Incidence of pulmonary hypertension, and the composite of pulmonary hypertension and PE recurrence. | Pulmonary hypertension: 16 vs. 57%, P <0.001 Composite: 16 vs. 63%, P <0.001 |
Unusual high rates of pulmonary hypertension, as a surrogate endpoint |
| Kucher et al (22), 2014 | Echocardiographic RV/LV ratio >1.0 | 59 | rt-PA (10 to 20 mg through PA catheter) |
Placebo | 63 (14) | 90 | 28 (47.5) | RV/LV ratio at 24 hours vs. baseline | CDT group: 1.28 vs. 0.99; P <0.001. Heparin group: 1.20 vs. 1.17; P =0.31). |
Not powered for clinical outcomes |
a
Patients also received standard anticoagulation.
Abbreviations: RV, right ventricle; CT, computed tomography; cTnI, cardiac troponin I; OR, odds ratio; BNP, brain natriuretic peptide; NT-proBNP, N-terminal pro-brain natriuretic peptide; VTE, venous thromboembolism; PE, pulmonary embolism; t-PA, tissue plasminogen activator; LV, left ventricle; CDT, catheter-directed thrombolysis.