Janssen 39039039APE4001

Principal Investigator: James Fair
Keywords: Rivaroxaban , pulmonary embolism Department: Emergency Medical Physicians
IRB Number: 00088529 Co Investigator:  
Specialty: Emergency Medicine, Pulmonary
Sub Specialties: Pulmonary
Recruitment Status: Recruiting

Contact Information

Steven Rondina
steven.rondina@hsc.utah.edu
801 587 0050

Brief Summary

Primary Objective

The primary objective of the study is to demonstrate that low risk PE patients who are discharged

from the ED to the home environment and treated with rivaroxaban as outpatients have fewer

total days in the hospital for bleeding and/or VTE events through Day 30 compared to patients

who are treated with initial hospitalization and standard-of-care.

Secondary Objective

The secondary objective of the study is to assess the reoccurrence of symptomatic, objectively

confirmed VTE, defined as recurrent PE or new or recurrent DVT (including symptomatic upper

extremity DVT) or VTE related death within 90 days of randomization.

Exploratory Objective

The exploratory objective of this study is to evaluate patient outcomes by baseline risk factors.

Inclusion Criteria

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study. Each

subject must:

1. Be a man or woman ≥18 years of age.

2. Have confirmed acute symptomatic PE with or without symptomatic DVT.

3. Be a PE patient diagnosed in the ED who is deemed to be at low risk of clinical

deterioration as determined by the Hestia criteria.

Note: Pulmonary embolism diagnosis is defined as the acute onset of dyspnea, chest

pain, dizziness, tachycardia, and/or palpitations confirmed per local standard-of-care

with imaging techniques such as Computed Tomography (CT), Pulmonary

Angiography, or Pulmonary Ventilation/Perfusion scan.

4. Have no contraindications to and be able to complete randomized treatment and all

study assessments.

5. Be able to be randomized within 12 hours after confirmation of PE diagnosis and be

assessed as able to be discharged from the ED after the initiation of randomized therapy.

6. Before randomization, a woman must be either:

! Not of childbearing potential: premenarchal; postmenopausal (>45 years of age

with amenorrhea for at least 12 months; permanently sterilized (eg, bilateral tubal

occlusion [which includes tubal ligation procedures as consistent with local

regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or

otherwise be incapable of pregnancy,

! Of childbearing potential and practicing a highly effective method of birth control

consistent with local regulations regarding the use of birth control methods for

subjects participating in clinical studies: eg, established use of oral, injected or

implanted hormonal methods of contraception; placement of an intrauterine device

or intrauterine system; barrier methods: condom with spermicidal

foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault

caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization

(the vasectomized partner should be the sole partner for that subject); true

abstinence (when this is in line with the preferred and usual lifestyle of the subject).

Note: If the childbearing potential changes after start of the study (eg, woman who

is not heterosexually active becomes active, premenarchal woman experiences

menarche) a woman must begin a highly effective method of birth control, as

described above.

7. A woman of childbearing potential must have a negative urine pregnancy test at

screening. Serum pregnancy testing may be performed if required by local regulation.

8. Subject must be willing and able to adhere to the prohibitions and restrictions specified

in this protocol.

9. Subject must have a life expectancy of at least 6 months.

10. Each subject must sign an informed consent form (ICF) indicating that he or she

understands the purpose of and procedures required for the study and are willing to

participate in the study.

 

 

Exclusion Criteria

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating

in the study. The subject will be excluded if he or she:

1. Answers YES to any of the Hestia criteria questions below:

! Include the following criteria but left to the discretion of the investigator:

Hemodynamically unstable as determined by the following: systolic blood

pressure <100 mm Hg with heart rate >100 bpm; condition requiring admission

to an intensive care unit.

! Thrombolysis or embolectomy necessary.

! Active bleeding or high risk for bleeding as determined by the following:

gastrointestinal bleeding in the preceding 14 days, recent stroke (less than 4

weeks ago) recent operation (less than 2 weeks ago), bleeding disorder or

thrombocytopenia (platelet <75,000 at screening), uncontrolled hypertension

(systolic >180 mm Hg or diastolic >110 mm Hg at screening).

! Oxygen supply to maintain oxygen saturation > 90% >24 hours.

! Pulmonary embolism diagnosed during anticoagulant treatment.

! Intravenous pain medication >24 hours.

! Medical or social reason for treatment in the hospital >24 hrs

! Creatinine clearance of less than 30 mL/min(calculated using the Cockroft Gault

formula using actual body weight) at screening. (See Attachment 5)

! Severe liver impairment; left to the discretion of the investigator

! Pregnant

! Documented history of heparin-induced thrombocytopenia

2. Combined P-gp and strong CYP3A4 inhibitors (such as but not limited to ketoconazole,

telithromycin or protease inhibitors) use within 4 days before randomization, or planned

use during the study. Itraconazole use within 7 days before randomization or planned

use during the study.

3. Combined P-gp and strong CYP3A4 inducers (such as but not limited to

rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or

St. John's Wort) use within 2 weeks before randomization or planned use during the

study.

4. Has contraindications to the use of any anticoagulant therapy (eg, bleeding diathesis,

history of gastrointestinal bleeding within 1 year or coagulopathy documented at

screening).

5. Has known allergies, hypersensitivity, or intolerance to rivaroxaban or its excipients

(refer to Investigator's Brochure).14

6. Has a history of malignancy within 1 year before screening (exceptions are squamous

and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy

that in the opinion of the investigator, with concurrence with the sponsor's medical

monitor, is considered cured with minimal risk of recurrence). Actively receiving

treatment for cancer or patients undergoing treatment for cancer or palliative care or CT

evidence suggesting undiagnosed malignancy.

7. Has elevated troponin levels at screening ≥99th percentile for normal control patients.

8. Has received an investigational drug (including investigational vaccines) or used an

invasive investigational medical device within 30 days before the planned first dose of

study drug.

9. Has taken any disallowed therapies as noted in Section 8, Pre-study and Concomitant

Therapy before the planned first dose of study drug.

10. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant.

11. Has any barriers to treatment adherence or follow up (ie. alcohol abuse, illicit drug use,

psychosis, dementia). Patients with insufficient social support for outpatient treatment,

which will include patients unlikely to have successful follow up (homeless and

prisoners) are not eligible for participation.

12. Has any condition for which, in the opinion of the investigator, participation would not

be in the best interest of the subject (eg, compromise the well-being) or that could

prevent, limit, or confound the protocol-specified assessments.

13. Had major surgery, (eg, requiring general anesthesia) within 14 days before screening,

or will not have fully recovered from surgery, or has surgery planned during the time the

subject is expected to participate in the study.

Note: subjects with planned surgical procedures to be conducted under local anesthesia

may participate.

14. Is an employee of the investigator or study site, with direct involvement in the proposed

study or other studies under the direction of that investigator or study site, as well as

family members of the employees or the investigator.

15. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests

positive for HIV at screening.