Standard-dose Apixaban AFtEr Very Low-dose ThromboLYSis for Acute Intermediate-high Risk Acute Pulmonary Embolism

• Status: Terminated
• Trial end date: 2020-04-05
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to examine the degree to which pulmonary embolism (clot) can be dissolved when treated with a very low dose of a systemic thrombolytic drug (clot buster) along with standard anticoagulant therapy as compared to the standard of care anticoagulant therapy alone.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Victor Tapson, MD
• Collaborator: Bristol-Myers Squibb
• Treatments: Apixaban; Calcium heparin; Heparin; Plasminogen; Tissue Plasminogen Activator

Criteria

Inclusion Criteria:

• Chest CT angiogram (CTA) evidence of proximal Pulmonary Embolism (PE) with a filling defect in at least one main pulmonary artery or lobar artery

• PE symptom duration ≤14 days

• Intermediate-high risk PE: defined as RV dysfunction with an RV/LV diameter ≥ 0.9, sPESI > 0, and either troponin > 0.05ng/mL or BNP > 100 pg/mL, and hemodynamically stable (systolic blood pressure > 90mmHg without the use of vasopressor support)

• Randomization within 24 + 4 hours of anticoagulation

• Signed and dated informed consent obtained from subject or legally authorized representative before initiation of any study procedures

Exclusion Criteria:

• Weight > 130kg or < 40 kg on day of randomization

• Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year

• Recent (within one month) or active bleeding from a major organ

• Major surgery within 14 days

• Clinician deems the subject too high-risk for bleeding using HAS-BLED criteria

• History of any hematologic disease or coagulopathy

• Cirrhosis (as determined by Child-Pugh B or C)

• History of heparin-induced thrombocytopenia (HIT)

• Hemodynamic instability defined as systolic blood pressure (SBP) less than 90mmHg and/or use of vasopressors for greater than 15 minutes

• Severe hypertension as defined as SBP greater than 180mmHg

• Cardiac arrest or active cardiopulmonary resuscitation (CPR)

• Receiving neuraxial anesthesia or undergoing spinal puncture

• Patient with prosthetic heart valves

• Evidence of irreversible neurological compromise

• Evidence of poor functional status

• History of major gastrointestinal bleed within the last month

• Active gastric or duodenal ulcers

• Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to diagnosis

• Lovenox administration within 12 hours of randomization

• Direct-acting oral anticoagulant use (dabigatran, rivaroxaban, apixaban, or edoxaban) with last known dose within 48 hours

• Hemoglobin < 10 g/dL

• Creatinine clearances < 60 mL/min

• Platelets < 100 thousand/µL

• INR > 1.4

• Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2 times upper limit of normal (ULN)

• Total bilirubin (TBL) ≥ 1.5 times ULN (except due to confirmed Gilbert's syndrome)

• Patient is pregnant (positive pregnancy test; women of childbearing capacity must be tested prior to enrollment) or breast feeding

• Patient who is a prisoner, or if subject who becomes compulsory detained

• Active cancer defined as diagnosis of cancer within six months before the study inclusion, or receiving treatment for cancer at the time of inclusion or any treatment for cancer during 6 months prior to randomization, or recurrent locally advanced or metastatic cancer

• Known allergy, hypersensitivity or thrombocytopenia from heparin, tPA, or apixaban or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be administered within 12 hours prior to the CTA

• HIV/AIDS