Efficacy and safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism
- Conditions
- Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]Venous Thromboembolism (VTE)MedDRA version: 14.0Level: PTClassification code 10037377Term: Pulmonary embolismSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersMedDRA version: 14.0Level: PTClassification code 10051055Term: Deep vein thrombosisSystem Organ Class: 10047065 - Vascular disorders
- Registration Number
- EUCTR2007-004953-27-AT
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2430
1) Signed Written Informed Consent
2) Target Population
a) Subjects who have:
• an unprovoked index event OR a provoked index event with a risk for
recurrence as described in the eligibility checklist
• an objectively documented index event of symptomatic proximal DVT
or symptomatic PE;
(1) Symptomatic proximal DVT is defined as symptomatic DVT with
evidence of proximal thrombosis that involves at least the popliteal vein
or a more proximal vein, demonstrated by imaging with compression
ultrasound (CUS), including grey-scale or color-coded Doppler, or
ascending contrast venography.
(2) Symptomatic PE with evidence of thrombosis demonstrated by
imaging as follows:
- an intraluminal filling defect in segmental or more proximal branches
on spiral CT scan; or
- an intraluminal filling defect or a sudden cutoff of vessels more than
2.5 mm in diameter on the pulmonary angiogram; or
- a perfusion defect of at least 75% of a segment with a local normal
ventilation result (high-probability) on ventilation/perfusion lung scan
(VPLS)
completed approximately 6 to 12 months of standard anticoagulant
therapy, or completed assigned CV185056 (AMPLIFY) study treatment,
for the treatment of the index event; and
• no objectively documented symptomatic recurrence of VTE after the
index event.
b) Subjects should be randomized within approximately 7 days of the
last dose of their initial 6-to 12-month treatment. If a VKA was used as
standard anticoagulant therapy, then an INR must be documented as 2
or less before randomization. If the subject received CV185056
(AMPLIFY) study treatment, then a blinded INR must be documented as
2 or less before randomization.
Every attempt should be made to randomize subjects as soon as possible
after discontinuation of their initial treatment.
The index DVT and/or PE will be adjudicated by the ICAC according to
the adjudication manual. Investigators are encouraged to assemble and
to submit imaging dossiers to the ICAC as soon as possible during the
period that extends from the beginning of the screening period up to 2
weeks after randomization.
3) Age and Sex
a) Men and women, ages 18 years or greater.
Women of childbearing potential (WOCBP) must be using an adequate
method of contraception to avoid pregnancy throughout the study in
such a manner that the risk of pregnancy is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method of
birth control to avoid pregnancy for the entire study
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to
investigational product administration
2) Medical History and Concurrent Diseases
a) Subjects with a provoked index event without the existence of a
persistent risk factor for recurrence as described in the eligibility
checklist.
b) More than 12 months of anticoagulation planned for the most recent
DVT or PE (index event).
c) Subjects with indications for long-term treatment with a VKA, such
as:
• Mechanical valve
• Atrial fibrillation or atrial flutter with moderate to high risk of systemic
thromboembolism
• Multiple episodes of unprovoked DVT or PE
• Documented anti-phospholipid antibodies, anti-thrombin III
deficiency, protein C deficiency, protein S deficiency, homozygous factor
V Leiden, or homozygous prothrombin gene mutation.
d) Subjects with cancer who will be treated indefinitely with
anticoagulation therapy;
e) Serious bleeding prior to randomization (see table under Protocol
section 4.2.2 for exact timing of occurence resulting in subject exclusion
from the study);
f) Active and clinically significant liver disease (eg, hepatorenal
syndrome);
g) Life expectancy < 12 months;
h) Bacterial endocarditis;
i) Uncontrolled hypertension: systolic blood pressure >180 mm Hg or
diastolic blood pressure >100 mm Hg.
3) Physical and Laboratory Test Findings
a) Platelet count <100,000/mm3;
b) Hemoglobin <9 g/dL;
c) Serum creatinine >2.5 mg/dL [221 umol/L];
d) Calculated creatinine clearance <25 ml/min. (see Section 6.3.2.2.);
e) ALT or AST >2 times upper limit of normal;
f)Total bilirubin >1.5 times upper limit of normal (unless an alternative
causative factor is identified [eg, Gilbert's syndrome]).
4) Prohibited Treatments and/or Therapies
a) Subjects requiring ASA >165 mg/day at randomization.
b) Subjects requiring dual anti-platelet therapy (such as ASA plus
clopidogrel or ASA plus ticlopidine) at randomization. Subjects who
transition from dual anti-platelet therapy to monotherapy prior to
randomization will be eligible for the trial.
c) Subjects who have used any oral direct factor Xa inhibitor, any oral
direct thrombin inhibitor, or any investigational antithrombotic agent
during the period between the onset of the index event to
randomization. Subjects who participated in the CV185056 (AMPLIFY)
study may participate in this study and are exempt from this exclusion
(see Section 5.7)
5) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a
psychiatric or physical (eg, infectious disease) illness
c) eceiving concurrent investigational agents or has received an
investigational agent within the past 30 days prior to the first dose of
study treatment (with the exception of approved medications being used
for an approved indication, eg, investigating a new dosing regimen for
an approved indication).
Subjects who participated in the CV185056 (AMPLIFY) study may
participate in this study and are exempt from this exclusion (see Section
5.7)
d) Any condition, which in the opinion of the investigator, would put the
subject at an unacceptable risk from participating in the study; or
e) Any other medical, social, logistical, o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method