Summary of studies using catheter-directed therapies (CDT) in patients with acute pulmonary embolism (PE)
| Trial name | Year | Sample Size | Population | Intervention | Control | Primary outcome | Efficacy | Safety |
| Randomised controlled trials testing the efficacy and safety of different modes of catheter-directed thrombolysis | ||||||||
| ULTIMA [14] | 2014 | 59 | Intermediate–high risk | USAT, EkoSonic Endovascular System (10 mg per 15 h) | Anticoagulation monotherapy | Change in 24-h TTE-based RV/LV ratio. | Mean RV/LV ratio was reduced 1.28 to 0.99 at 24 h (p<0.001) in USAT group versus 1.20 to 1.17 at 24 h (p=0.31) in heparin group | At 90 days, there was one death (control), no major bleeding, four minor bleeding episodes (three in the USAT group and one in the heparin group; p=0.61) |
| OPTALYSE PE [16] | 2018 | 100 | Intermediate risk | USAT, EkoSonic Endovascular System (4 mg per 2 h) (arm 1) | USAT, EkoSonic System (4 mg per 4 h) (arm 2) (6 mg per 6 h) (arm 3) (12 mg per 6 h) (arm 4) | Change in the 48-h CT-based RV/LV ratio | Mean RV/LV diameter ratio: Arm 1: 0.40 (24.0%) Arm 2: 0.35 (22.6%) Arm 3: 0.42 (26.3%) Arm 4: 0.48 (25.5%) | Major bleeding event rates: Arm 1: 0% Arm 2: 3.7% Arm 3: 3.6% Arm 4: 11.1% |
| SUNSET-sPE [17] | 2021 | 81 | Intermediate risk (submassive) | USAT, EkoSonic Endovascular System (8 mg per 8 h) | cCDT, UniFuse (AngioDynamics) or Cragg-McNamara (Medtronic) (8 mg per 8 h) | Change in the 48-h CT-based thrombus burden | No significant difference in mean thrombus burden. Mean reduction in RV/LV ratio (p=0.01): USAT: 0.37 cCDT: 0.59 | Major bleeds: intervention four versus control zero |
| CANARY [20] | 2022 | 94 | Intermediate-high risk | cCDT, Cragg-McNamara (Medtronic) (12 mg per 24 h) | Anticoagulation monotherapy | Proportion of patients with a TTE-based RV/LV ratio >0.9 at a 3-month follow-up | 4.3% in the cCDT group and 12.8% in the anticoagulation monotherapy group (p=0.24) Median RV/LV ratio at 3-month follow-up (p=0.01): cCDT: 0.7 Anticoagulation monotherapy: 0.8 | One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group |
| HI-PEITHO (NCT04790370) [21] | 406 | Intermediate–high risk with additional criteria of severity | USAT, EkoSonic Endovascular System (9 mg per 7 h) | Parenteral anticoagulation monotherapy | Composite of PE-related mortality, PE recurrence or cardiorespiratory decompensation or collapse, within 7 days of randomisation | Ongoing | Ongoing | |
| BETULA (NCT03854266) [24] | 60 | Intermediate–high risk | cCDT, Unifuse (AngioDynamics) (4 mg per 2 h) | Unfractionated heparin monotherapy | Improvement in RV/LV ratio at 24 h | Recruiting | Recruiting | |
| PE-TRACT (NCT05591118) [22] | 500 | Intermediate risk | CDT consisting of mechanical thrombectomy or cCDT | Anticoagulation monotherapy | Peak oxygen consumption at a 3-month follow-up | Ongoing | Ongoing | |
| PEERLESS (NCT05111613) [25] | 550 | Intermediate–high risk without absolute contraindication of thrombolysis | Mechanical thrombectomy, FlowTriever System | cCDT (any commercially available CDT system) | Composite clinical end-point of all-cause mortality, ICH, major bleeding, clinical deterioration, ICU admission, and ICU length of stay during hospitalisation | Recruiting | Recruiting | |
| STORM-PE (NCT05684796) [26] | 100 | Intermediate–high risk | Mechanical aspiration, Indigo Aspiration System | Anticoagulation monotherapy | Change in the 48-h CT-based RV/LV ratio | Recruiting | Recruiting | |
| STRATIFY (NCT04088292) [27] | 210 | Intermediate–high risk | USAT (20 mg per 6 h) | Anticoagulation monotherapy | Reduction in Miller score 48–96 h post-randomisation | Recruiting | Recruiting | |
| Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE (NCT03581877) [28] | 2023 | 31 | Intermediate risk | Peripheral low-dose thrombolysis (24 mg per 12 h) | USAT, EkoSonic Endovascular System (24 mg per 12 h) | Change in the 48-h TTE-based RV/LV ratio | Completed | Completed |
| Registry of prospective studies testing the efficacy and safety of different modes of catheter-directed thrombolysis | ||||||||
| SEATTLE II [15] | 2015 | 150 | Massive (n=31) Submassive (n=119) | USAT, EkoSonic Endovascular System (24 mg per 24 h) | Change in the 48-h CT-based RV/LV ratio | Mean RV/LV ratio decreased from 1.55 to 1.13 at 48 h (p<0.0001). | One GUSTO severe bleed; 16 GUSTO moderate bleed | |
| KNOCKOUT PE Registry [29] | 2018 | 1480 | Intermediate–high risk or high risk | USAT, EkoSonic Endovascular System | Change in 24–48 h TTE-based RV/LV ratio Persistence of pulmonary hypertension | Ongoing | Ongoing | |
| PERFECT [30] | 2015 | 101 | Massive (n=28) Submassive (n=73) | Massive PE: catheter-directed mechanical or pharmaco-mechanical thrombectomy Submassive PE: catheter-directed thrombolysis (UniFuse, EkoSonic or pig tail) | Clinical success was defined as: stabilisation of haemodynamic, improvement in pulmonary hypertension and/or right heart strain, and survival to hospital discharge | Clinical success: Massive PE: 85.7% (95% CI 67.3–96.0%) Submassive PE: 97.3% (95% CI 90.5–99.7%) | No major haemorrhages and no haemorrhagic strokes | |
| FLARE [31] | 2019 | 106 | Intermediate–high risk | Mechanical thrombectomy, FlowTriever System (Inari) | Change in the 48-h CT-based RV/LV ratio | Mean RV/LV ratio 1.53 reduced to 1.15 at 48 h | Four patients (3.8%) experienced six major adverse events | |
| EXTRACT-PE [32] | 2021 | 119 | Submassive PE | Mechanical aspiration, IndigoVac (Penumbra) | Change in the 48-h CT-based RV/LV ratio | Mean RV/LV ratio reduction was 0.43 (95% CI 0.38–0.47; p<0.0001) at 48 h | Two (1.7%) patients experienced three major adverse events | |
| FLAME [18] | 2023 | 115 | High-risk PE | Mechanical thrombectomy, FlowTriever System (Inari) | Context arm | Composite incidence of all-cause mortality, clinical deterioration, bailout, and major bleeding at 45 days | FlowTriever: 17% Context arm: 63.9% | |
| FLASH interim results registry [33] | 2022 | 250 | Intermediate–risk (n=233) High risk (n= 17) | Mechanical thrombectomy, FlowTriever System (Inari) | Composite of MAEs: device-related death, major bleeding, and intraprocedural device- or procedure-related adverse events at 48 h | MAEs: three (1.2%), all of which were major bleeds that resolved without sequelae All-cause mortality was 0.4% at 30 days, with a single death that was unrelated to PE | ||
| FLASH 6 months [34] | 2023 | 799 | High risk (n=64) Intermediate–high risk (n=616) Intermediate–low risk or unclassified (n=119) | Mechanical thrombectomy, FlowTriever System (Inari) | Evaluate RV function, MMRCD, 6MWT distances, and PE QoL scores at 6 months | Normal RV function increased from 15.1% to 95.1% (p<0.0001) MMRCD score improved from 3.0 to 0.0 (p<0.0001) 6MWT distances increased from 180 m to 398 m (p <0.001) | Prevalence of site-reported chronic thromboembolic pulmonary hypertension was 1.0% and chronic thromboembolic disease was 1.9% | |
| FLASH full cohort [19] | 2023 | 800 | High risk (n=63) Intermediate–high risk (n=614) | Mechanical thrombectomy, FlowTriever System (Inari) | Composite of MAE: device-related death, major bleeding, device- or procedure-related adverse events | MAEs: 1.8% All-cause mortality was 0.3% at 48-h follow-up and 0.8% at 30-day follow-up, with no device-related deaths | ||
RV: right ventricular; LV: left ventricular; TTE: transthoracic echocardiogram; CT: computed tomography; cCDT: combined catheter-directed treatment (fibrinolysis and thrombectomy); GUSTO: Global Use of Streptokinase and t-PA for Occluded Coronary Arteries; ICH: intracerebral haemorrhage; ICU: intensive care unit; MAE: major adverse events; MMRCD: modified Medical Research Council dyspnoea scores; 6MWT: 6-min walk test; QoL: quality of life.