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

NCT03988842 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: Pro00054951
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Embolism With Acute Cor Pulmonale; Pulmonary Embolism; Pulmonary Embolism With Pulmonary Infarction; Pulmonary Embolism Subacute Massive; Right Ventricular Dysfunction; Right Ventricular Failure

Outcome Measures

Primary Outcomes (1)

• Change in Extent of Clot Lysis in the Experimental Arm

  Change in percentage of clot lysis in the experimental arm only as measured using the Refined Modified Miller Score (RMMS) from the baseline CTA to the 24 hour CTA after 24mg of systemic (IV) tPA + standard anticoagulation therapy (experimental arm).

  Baseline, 24 hours

Secondary Outcomes (11)

• Change in Extent of Clot Lysis Between the Experimental Arm and the Active Comparator Arm

  Baseline, 24 hours

• Change in Right Ventricular to Left Ventricular Diameter (RV/LV) Ratio

  Baseline, 24 hours

• Change in RV/LV Ratio From Baseline Echocardiogram

  Baseline, 24 hours and 30 days

• Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) From Baseline Echocardiogram

  Baseline, 24 hours and 30 days

• Change in Right Ventricular Systolic Pressure (RVSP) From Baseline Echocardiogram

  Baseline, 24 hours and 30 days

Study Arms (2)

Alteplase & Unfractionated Heparin & Apixaban

EXPERIMENTAL

Alteplase 24mg intravenous infusion for 20 minutes followed by unfractionated heparin intravenous infusion over 24 hours followed by apixaban 10mg tablet twice-daily for one week followed by apixaban 5mg tablet twice-daily for at least 6 months.

Drug: Alteplase; Drug: Unfractionated heparin; Drug: Apixaban

Placebo & Unfractionated Heparin & Apixaban

ACTIVE COMPARATOR

Alteplase placebo solution 24mg intravenous infusion for 20 minutes followed by unfractionated heparin intravenous infusion over 24 hours followed by apixaban 10mg tablet twice-daily for one week followed by apixaban 5mg tablet twice-daily for at least 6 months.

Drug: Unfractionated heparin; Drug: Placebo; Drug: Apixaban

Interventions

Alteplase DRUG

Lyophilized powder for reconstitution in 50mg vials

Also known as: Activase, tissue-type plasminogen activator

Alteplase & Unfractionated Heparin & Apixaban

Unfractionated heparin DRUG

Heparin sodium in 0.45% sodium chloride injection for intravenous use

Also known as: Heparin sodium

Alteplase & Unfractionated Heparin & Apixaban; Placebo & Unfractionated Heparin & Apixaban

Placebo DRUG

Saline solution reconstituted to mimic Alteplase 50mg vial

Also known as: Placebo (for Alteplase)

Placebo & Unfractionated Heparin & Apixaban

Apixaban DRUG

Apixaban tablet

Also known as: Eliquis

Alteplase & Unfractionated Heparin & Apixaban; Placebo & Unfractionated Heparin & Apixaban

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Victor Tapson, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

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  BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism; Ventricular Dysfunction, Right; Heart Failure

Interventions

Tissue Plasminogen Activator; Heparin; apixaban

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Heart Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

Enrollment was held and study closed prematurely due to COVID-19 pandemic. We were otherwise hopeful to enroll and complete all assessments for this study.

Results Point of Contact

• Title: Victor Tapson
• Organization: Cedars-Sinai Medical Center

Victor.Tapson@cshs.org

919-971-6441

Study Officials

• Victor F Tapson, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Aaron S Weinberg, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Clinical Research for the Women's Guild Lung Institute; Director, Venous Thromboembolism and Pulmonary Vascular Disease Research Program; Associate Director, Pulmonary and Critical Care Division

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 18, 2019
• Study Start: July 25, 2019
• Primary Completion: April 5, 2020
• Study Completion: April 5, 2020
• Last Updated: June 11, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)