Low Dose Catheter Directed Thrombolysis for Acute Intermediary-high Risk Pulmonary Embolism

1. Aim To investigate if low dose catheter directed fibrinolysis for 2 hours is superior to unfractioned heparin with regards to unloading the right ventricle in acute intermediate-high risk pulmonary embolism
2. Methods 2.1 Study design The study is an open label, randomized, single center trial. Patients (n=60) with acute intermediate-high risk acute pulmonary embolism diagnosed with computed tomography pulmonary angiography (CTA) will be treated with unfractionated heparin (UFH) at the time of diagnosis and randomized 1:1 within 48 h to low dose catheter directed thrombolysis or continuation of UFH. Primary endpoint is improvement in right-to-left ventricular ratio (RV/LV ratio) evaluated by CTA 24 hours (±2h) after randomization. Secondary endpoints are 30 day mortality, reduction in thrombus burden evaluated by CTA, length of hospital stay and recurrent PE. Safety will be monitored as minor and major bleeding.

2.2 Patients Patients are eligible for inclusion if they apply to all inclusion and none of the exclusion criteria and give their informed written consent

2.2.1 Recruitment and informed consent Patients admitted to a hospital in Region Midt with acute pulmonary embolism will be screened for eligibility for inclusion in the trial by a local investigator at the day of admission. The local investigator will then contact the PI that will ensure that the patient is eligible for inclusion. All patients referred for possible inclusion will be registered as screened. If eligible for inclusion, the local investigator will give the verbal and written study information to the patient. The local investigator will do the best possible to avoid interruptions and the staff will be informed accordingly to ensure fewest possible interruptions during the verbal information. The patient will be informed that it is possible to have an assessor during the verbal information. After verbal and written information the patient will be given a minimum of 1/2 hour and up to 8 hours for reflection before giving their consent. The patient will also be informed, that they can withdraw their consent at any time.

2.2.2 Benefits, risk and safety The patients included in this trial will be treated with the highest known standard of care for their acute PE. If randomized to conventional treatment (UFH), there is no obvious benefit for the individual patient with regards to treatment, but the extra diagnostics may aid the treating physician to optimize their standard treatment. For patients randomized to CDT there is a potential benefit of treatment due to faster removal of thrombus mass in the pulmonary arteries. The biggest advantage of this trial is for future patients with acute PE, as this trial will aid future decisions with regards to treatment with CDT or UFH. Safety is discussed in section 12.

2.2.3 Patient discontinuation and substitution Patients that are included in the study but discontinue (any cause) before their follow-up CTA 24 hours after treatment will be excluded from the final data analysis and substituted by a new study patient. Data from patients that discontinue (any cause) after their follow-up 24 hours CTA will be included in the final analysis. Data from patients that withdraw their consent for study participation will be excluded and substituted by a new study patient, if the trial is still ongoing at time of withdrawal.