Clot Dissolving Treatment for Blood Clots in the Lungs
Condition: Pulmonary Embolism
MeSH terms: Pulmonary Embolism; Embolism
Intervention: Tenecteplase + Enoxaparin; 0.9% Saline + Enoxaparin
Intervention description: Enoxaparin: 1 mg/kg within 12 hours before receiving tenecteplase.Subsequently, patients will receive 1 mg/kg enoxaparin SQ Q12 hours until discontinuation is clinically indicated.
Tenecteplase:will be administered using a tiered-dosing schedule according to patient weight: <60Kg=30mg; ≥60Kg to <70Kg=35mg; ≥70Kg to <80Kg=40mg; ≥80Kg to <90Kg=45mg; ≥90Kg=50mg; Enoxaparin: 1 mg/kg within 12 hours before receiving saline.
Intervention MeSH terms: Enoxaparin; Tenecteplase; Enoxaparin sodium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pulmonary Embolism; Tenecteplase; Enoxaparin; Thrombosis; Fibrinolytics

Summary:

      The purpose of this study is to determine if tenecteplase plus enoxaparin is safe and
      effective in the treatment of patients with severe submassive pulmonary embolism.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pulmonary vascular imaging positive for PE within the previous 24 hours

          -  Ability to provide written informed consent and comply with study assessments for the
             full duration of the study

          -  Age >17 years

          -  Evidence of severe PE: RV hypokinesis on echocardiography, abnormal troponin I or T
             (any non-normal including indeterminate values, using local reference thresholds) or
             BNP measurement >90 pg/mL or NT proBNP >900 pg/ml (not more than 6 hours prior to CT
             angiography and not more than 30 hours before enrollment) or a pulse oximetry reading
             <95% within previous two hours (<93% in Denver).

        Exclusion Criteria:

          -  Systolic blood pressure < 90 mm Hg at time of informed consent

          -  Do not resuscitate or do not intubate order

          -  Systemic fibrinolytic treatment within previous 7 days

          -  Inability to follow-up at 3 months

          -  Documented gastrointestinal bleeding within previous 30 days

          -  Active hemorrhage in any of the following sites at the time of enrollment:
             intraperitoneal, retroperitoneal, pulmonary, uterine, bladder, or nose.

          -  Head trauma causing loss of consciousness within previous 7 days

          -  Any history of hemorrhagic stroke

          -  Ischemic stroke within the past year

          -  Prior history of heparin-induced thrombocytopenia

          -  History of intraocular hemorrhage

          -  Intracranial metastasis

          -  Known inherited bleeding disorder, e.g., hemophilia

          -  Platelet count < 50,000/uL

          -  Prothrombin time with an INR >1.7

          -  Chest, abdominal, intracranial or spinal surgery within the previous 14 days

          -  Subacute bacterial endocarditis

          -  Pregnancy (positive pregnancy test)

          -  Prior enrollment in the study

          -  Current treatment with fondiparinux, dalteparin, a direct thrombin inhibitor or
             administration of a glycoprotein inhibitor within the previous 48 hours.

          -  Known pericarditis

          -  Allergy to heparins,or tenecteplase

          -  Elapsed time that would preclude drug or placebo administration within 24 hours after
             diagnosis

          -  Evidence of non-end stage kidney injury (creatinine clearance < 30 ml/min without
             chronic hemodialysis treatment; chronic hemodialysis-treated patients are eligible)

          -  Preexisting end-stage cardiopulmonary disease (heart failure with left ventricular
             ejection fraction <20%, known severe pulmonary hypertension or other lung disease
             causing permanent dependence upon oxygen)

          -  Any other condition that the investigator believes would pose a significant hazard to
             the subject