Summary of studies using catheter-directed therapies (CDT) in patients with acute pulmonary embolism (PE)

Trial nameYearSample SizePopulationInterventionControlPrimary outcomeEfficacySafety
Randomised controlled trials testing the efficacy and safety of different modes of catheter-directed thrombolysis
 ULTIMA [14]201459Intermediate–high riskUSAT, EkoSonic Endovascular System (10 mg per 15 h)Anticoagulation monotherapyChange 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 groupAt 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]2018100Intermediate riskUSAT, 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 ratioMean 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]202181Intermediate 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 burdenNo 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]202294Intermediate-high riskcCDT, Cragg-McNamara (Medtronic) (12 mg per 24 h)Anticoagulation monotherapyProportion of patients with a TTE-based RV/LV ratio >0.9 at a 3-month follow-up4.3% 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]406Intermediate–high risk with additional criteria of severityUSAT, EkoSonic Endovascular System (9 mg per 7 h)Parenteral anticoagulation monotherapyComposite of PE-related mortality, PE recurrence or cardiorespiratory decompensation or collapse, within 7 days of randomisationOngoingOngoing
 BETULA  (NCT03854266)  [24]60Intermediate–high riskcCDT, Unifuse (AngioDynamics) (4 mg per 2 h)Unfractionated heparin monotherapyImprovement in RV/LV ratio at 24 hRecruitingRecruiting
 PE-TRACT  (NCT05591118)  [22]500Intermediate riskCDT consisting of mechanical thrombectomy or cCDTAnticoagulation monotherapyPeak oxygen consumption at a 3-month follow-upOngoingOngoing
PEERLESS (NCT05111613) [25]550Intermediate–high risk without absolute contraindication of thrombolysisMechanical thrombectomy, FlowTriever SystemcCDT (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 hospitalisationRecruitingRecruiting
 STORM-PE  (NCT05684796)  [26]100Intermediate–high riskMechanical aspiration, Indigo Aspiration SystemAnticoagulation monotherapyChange in the 48-h CT-based RV/LV ratioRecruitingRecruiting
 STRATIFY  (NCT04088292)  [27]210Intermediate–high riskUSAT (20 mg per 6 h)Anticoagulation monotherapyReduction in Miller score 48–96 h post-randomisationRecruitingRecruiting
 Peripheral  Systemic  Thrombolysis Versus Catheter  Directed  Thrombolysis  for Submassive PE (NCT03581877)  [28]202331Intermediate riskPeripheral 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 ratioCompletedCompleted
Registry of prospective studies testing the efficacy and safety of different modes of catheter-directed thrombolysis
 SEATTLE II [15]2015150Massive (n=31)
Submassive  (n=119)
USAT, EkoSonic Endovascular System (24 mg per 24 h)Change in the 48-h CT-based RV/LV ratioMean 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]20181480Intermediate–high risk or high riskUSAT, EkoSonic Endovascular SystemChange in 24–48 h TTE-based RV/LV ratio
Persistence of pulmonary  hypertension
 PERFECT [30]2015101Massive (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 dischargeClinical 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]2019106Intermediate–high riskMechanical thrombectomy, FlowTriever System (Inari)Change in the 48-h CT-based RV/LV ratioMean RV/LV ratio 1.53 reduced to 1.15 at 48 hFour patients (3.8%) experienced six major adverse events
 EXTRACT-PE [32]2021119Submassive PEMechanical aspiration, IndigoVac (Penumbra)Change in the 48-h CT-based RV/LV ratioMean RV/LV ratio reduction was 0.43 (95% CI 0.38–0.47; p<0.0001) at 48 hTwo (1.7%) patients experienced three major adverse events
 FLAME [18]2023115High-risk PEMechanical thrombectomy, FlowTriever System (Inari)Context armComposite incidence of all-cause mortality, clinical deterioration, bailout, and major bleeding at 45 daysFlowTriever: 17%
Context arm: 63.9%
 FLASH interim  results registry [33]2022250Intermediate–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 hMAEs: 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]2023799High 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 monthsNormal 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]2023800High 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 eventsMAEs: 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.