Prospective Multicenter International Registry of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Intermediate-High and High-Risk Pulmonary Embolism (KNOCOUT PE).

BACKGROUND

Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes.

METHODS

The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months.

RESULTS

Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively.

CONCLUSIONS

In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low.

REGISTRATION

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.

Déclaration de conflit d'intérêts

At the time of KNOCOUT (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) and writing of this article, Dr Sterling was a consultant to Boston Scientific, Access Vascular Inc, and vizai. Dr Sterling is now an employee of Boston Scientific. Dr Piazza has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, NAMSA, Penumbra, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. Dr Sharp was a Consultant to Medtronic, Boston Scientific, Recor Medical, Penumbra, Philips. Dr Kucher received consulting and lecture fees from Concept Medical, Boston Scientific, Bayer, and INARI; institutional grants from the Swiss National Foundation, Bard, Bayer, Boston Scientific, Concept Medical, and Sanofi; not related to the present work. Dr Goldhaber received Research Support from Bayer, BMS, Boston Scientific, Janssen, NHLBI, and Pfizer. Dr Meneveau was a consultant at Abbott Medical, Bayer Health Care, Bristol-Myers Squibb, Edwards Lifesciences, Terumo, Inari, Boston Scientific. Fees: Abbott Medical, AstraZeneca, Bayer Health Care, Bristol-Myers Squibb, Pfizer, Terumo. Dr Zlotnick participated in Speaker’s Bureau: Abiomed, Inari Medical; Consultant/Speaker’s Bureau: Angiodynamics. Dr Sayfo was consultant with Boston Scientific. Dr Konstantinides received institutional grants from Bayer AG, Daiichi-Sankyo, and Boston Scientific; consulting or lecture fees from Bayer AG, Daiichi Sankyo, Boston Scientific, Penumbra, MSD, Pfizer, and Bristol-Myers Squibb. The other authors report no conflicts.