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Trial record 20 of 172 for:    "Heart Disease" | "Heparin"

Standard-dose Apixaban AFtEr Very Low-dose ThromboLYSis for Acute Intermediate-high Risk Acute Pulmonary Embolism (SAFE-LYSE)

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ClinicalTrials.gov Identifier: NCT03988842
Recruitment Status : Not yet recruiting
First Posted : June 18, 2019
Last Update Posted : June 18, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Victor Tapson, MD, Cedars-Sinai Medical Center

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.

Condition or disease Intervention/treatment Phase
Pulmonary Embolism With Acute Cor Pulmonale Pulmonary Embolism Pulmonary Embolism With Pulmonary Infarction Pulmonary Embolism Subacute Massive Right Ventricular Dysfunction Right Ventricular Failure Drug: Alteplase Drug: Unfractionated heparin Drug: Placebo Drug: Apixaban Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Standard-dose Apixaban AFtEr Very Low-dose ThromboLYSis for Acute Intermediate-high Risk Acute Pulmonary Embolism
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Alteplase & Unfractionated Heparin & Apixaban
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
Lyophilized powder for reconstitution in 50mg vials
Other Names:
  • Activase
  • tissue-type plasminogen activator

Drug: Unfractionated heparin
Heparin sodium in 0.45% sodium chloride injection for intravenous use
Other Name: Heparin sodium

Drug: Apixaban
Apixaban tablet
Other Name: Eliquis

Active Comparator: Placebo & Unfractionated Heparin & Apixaban
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
Heparin sodium in 0.45% sodium chloride injection for intravenous use
Other Name: Heparin sodium

Drug: Placebo
Saline solution reconstituted to mimic Alteplase 50mg vial
Other Name: Placebo (for Alteplase)

Drug: Apixaban
Apixaban tablet
Other Name: Eliquis




Primary Outcome Measures :
  1. Change in extent of clot lysis in the Experimental Arm [ Time Frame: Baseline, 24 hours ]
    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).


Secondary Outcome Measures :
  1. Change in extent of clot lysis between the Experimental Arm and the Active Comparator Arm [ Time Frame: Baseline, 24 hours ]
    Change in percentage of clot lysis between the experimental arm and the active comparator arm 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) compared to 24mg of systemic (IV) placebo + standard anticoagulation therapy (active comparator arm).

  2. Change in right ventricular to left ventricular diameter (RV/LV) ratio [ Time Frame: Baseline, 24 hours ]
    RV/LV ratio as measured by chest CTA from baseline to 24 ± 6 hours after the infusion of very low dose systemic (IV) tPA in patients with acute intermediate-high risk PE compared with placebo.

  3. Change in RV/LV ratio from baseline Echocardiogram [ Time Frame: Baseline, 24 hours and 30 days ]
    Change from baseline in echocardiographic parameters as measured by the RV/LV ratio within 24 hours ± 6 hours and at 30 ± 5 days after the end of the systemic (IV) tPA infusion compared with placebo.

  4. Change in tricuspid annular plane systolic excursion (TAPSE) from baseline Echocardiogram [ Time Frame: Baseline, 24 hours and 30 days ]
    Change from baseline in echocardiographic parameters as measured by the tricuspid annular plane systolic excursion (TAPSE) within 24 hours ± 6 hours and at 30 ± 5 days after the end of the systemic (IV) tPA infusion compared with placebo.

  5. Change in right ventricular systolic pressure (RVSP) from baseline Echocardiogram [ Time Frame: Baseline, 24 hours and 30 days ]
    Change from baseline in echocardiographic parameters as measured by the estimated right ventricular systolic pressure (RVSP) within 24 hours ± 6 hours and at 30 ± 5 days after the end of the systemic (IV) tPA infusion compared with placebo.

  6. Change in the collapse of the inferior vena cava (IVC) from baseline Echocardiogram [ Time Frame: Baseline, 24 hours and 30 days ]
    Change from baseline in echocardiographic parameters as measured by the collapse of the inferior vena cava (IVC) with respiration within 24 hours ± 6 hours and at 30 ± 5 days after the end of the systemic (IV) tPA infusion compared with placebo.

  7. Change in the requirement for oxygen therapy after 6 Minute Walk Test (6MWT) [ Time Frame: 30 days, 60 days, and 1 year ]
    6MWT distance as measured by the requirement for oxygen therapy at 30 day, 60 day and one year ± 14 days clinic follow-up compared with placebo.

  8. Change in Borg Dyspnea Scale score after 6 Minute Walk Test (6MWT) [ Time Frame: 30 days, 60 days, and 1 year ]
    6MWT distance as measured by the Borg Dyspnea Scale score (Borg score) at 30 day, 60 day and one year ± 14 days clinic follow-up compared with placebo. The Borg Scale measures self-reported intensity and severity of breathlessness (dyspnea) and fatigue before, during, and after a 6MWT. Each item is scored 0 - 10 (0 = no breathlessness at all; 10 = most severe breathlessness that you have ever experienced), yielding a total between 0 and 20.

  9. Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) questionnaire [ Time Frame: 30 days, 6 months, and 1 year ]
    Quality of life (QOL) as measured by the PROMIS PF-6at 30 days, 6 months and one year ± 14 days clinic follow-up compared with placebo. The PROMIS PF-6 measures self-reported physical function for everyday tasks (i.e., yard work, shopping, walking up/down stairs). Each item is score 1 - 5 (1 = unable to do/cannot do; 5 = without any difficulty/not at all), yielding a total between 6 and 30.

  10. Change in Pulmonary Embolism Quality of Life (PEmb-QOL) questionnaire [ Time Frame: 30 days, 6 months, and 1 year ]
    Quality of life (QOL) as measured by the PEmb-QOL at 30 days, 6 months and one year ± 14 days clinic follow-up compared with placebo. The PEmb-QOL measures self-reported QOL after a Pulmonary Embolism. The PEmb-QOL has nine sub-scales with higher scores indicating worse outcomes. Each item is score 1 - 5 (1 = unable to do/cannot do; 5 = without any difficulty/not at all), yielding a total between 6 and 30.

  11. Number of recurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) events [ Time Frame: 30 days, 60 days, 6 months, and 1 year ]
    Measured as the number of recurrent DVT and/or PE events in patients at 30 days, 60 days, 6 months, and 1 year compared to placebo.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03988842


Contacts
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Contact: Joseph Meza, BA 310-423-3598 ext 3-3598 Joseph.Meza@cshs.org
Contact: Niree Hindoyan, BS 310-423-4788 ext 3-4788 Niree.Hindoyan@cshs.org

Locations
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United States, California
Cedars-Sinai Medical Center Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Susan Jackman, RN, MS         
Sponsors and Collaborators
Victor Tapson, MD
Bristol-Myers Squibb
Investigators
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Principal Investigator: Victor F Tapson, MD Cedars-Sinai Medical Center
Principal Investigator: Aaron S Weinberg, MD Cedars-Sinai Medical Center

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Responsible Party: Victor Tapson, MD, 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, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT03988842     History of Changes
Other Study ID Numbers: Pro00054951
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Heart Disease
Heart Diseases
Heparin
Calcium heparin
Pulmonary Embolism
Pulmonary Infarction
Embolism
Ventricular Dysfunction
Ventricular Dysfunction, Right
Infarction
Ischemia
Pathologic Processes
Necrosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Tissue Plasminogen Activator
Apixaban
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors