A RANDOMIZED, OPEN-LABEL, ACTIVE CONTROLLED, SAFETY AND EXTRAPOLATED EFFICACY STUDY IN PEDIATRIC SUBJECTS REQUIRING ANTICOAGULATION FOR THE TREATMENT OF A VENOUS THROMBOEMBOLIC EVENT
- Conditions
- Venous ThromboembolismMedDRA version: 21.1Level: LLTClassification code 10043565Term: Thromboembolic eventSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2014-002606-20-GB
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
1.Children from birth to <18 years of age with a minimum weight of 2.6 kg at the time of randomization. An approved protocol will be implemented prior to enrollment of each subsequent age group.
Neonates are defined as infants from birth up to =27 days of life. For pre-term infants born between 34 and <37 weeks gestation, investigators have the option to define the 27 day neonatal period starting from the actual date of birth (post-natal age) or may choose to define the 27 day neonatal period starting when the postmenstrual age (gestational age plus the post-natal age) reaches 37 weeks and enroll the infant no more than 27 days thereafter into Cohort 4. Gestational age is the time elapsed between the first day of the last normal menstrual period and the day of delivery. Neonates or infants born prematurely at <34 weeks' gestation are excluded from this study until the age of = 6 months of life. Gestational age will only be taken into consideration for eligibility up to 6 months of age.
2.Presence of an index VTE which is confirmed by imaging. Index VTE include, but are not limited to, deep vein thrombosis, pulmonary embolus, cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related thrombosis and splanchnic thrombosis. In Germany only, cerebral sinovenous thrombosis will be excluded.
3.Intention to manage the index VTE with anticoagulation treatment for at least 12 weeks or intention to manage the index VTE with anticoagulation treatment in neonates (birth to 27 days) and children 28 days to <2 years of age for 6-12 weeks.
4.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Depending on local regulations, whenever the minor is able to give assent, the minor’s assent must also be obtained.
5.Subjects/legally acceptable representatives who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
6.For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective method of contraception throughout the study and for at least 33 days (5 half-lives plus 30 days) after the last dose of assigned treatment.
7. Subjects able to tolerate oral feeding, nasogastric (NG), gastric (G) feeding for at least 5 days.
Are the trial subjects under 18? yes
Number of subjects for this age range: 250
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Anticoagulant treatment for the index VTE for greater than 14 days prior to randomization. Neonates that are enrolled into the PK cohort must be on a minimum of 5 days and a maximum of 14 days SOC anticoagulation prior to randomization. Neonates that are enrolled into the post PK cohort may receive SOC anticoagulation for up to 14 days prior to randomization.
2. Cerebral sinovenous thrombosis (in Germany only).
3. Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE
4. A mechanical heart valve
5.Active bleeding or high risk of bleeding (e.g. central nervous system (CNS) tumors) at the time of randomization.
6.Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization.
7.Abnormal baseline liver function (ALT > 3 x upper limit of normal (ULN) or conjugated bilirubin > 2x ULN) at randomization.
8.At the time of randomization, inadequate renal function as defined in Section 7.2.2 Estimated Glomerular Filtration Rate Assessment of the protocol.
9.Platelet count < 50×109 per L at randomization.
10.At the time of randomization, uncontrolled severe hypertension as defined in Section 7.1 Physical Examination of the protocol.
11.At the time of randomization, use of prohibited concomitant medication as listed for apixaban in Section 5.5 Concomitant Medication of the protocol.
12.Known allergy to apixaban or any of the other ingredients in the apixaban formulation, or hypersensitivity to any of the components of the comparators.
13.Female subjects who are either pregnant or breastfeeding a child.
14.Geographically unavailable for follow-up.
15.Family members who are either investigational site staff members directly involved in the conduct of this trial or site staff members otherwise supervised by the Investigator. Family members who are Pfizer or Bristol Myers Squibb (BMS) employees directly involved in the conduct of this trial.
16.Taking an investigational drug in other studies within 30 days before the first dose of apixaban and/or during study participation. N.B. using marketed medications commonly used in usual and customary practice, though not labeled for use in children, is acceptable.
17.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
18. Use of aggressive life-saving therapies such as ventricular assist
devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the
time of enrollment.
19. Unable to take oral or enteric medication via the NG or G tube.
20. Known inherited or acquired antiphospholipid syndrome (APS).
21. Known inherited bleeding disorder or coagulopathy with increased
bleeding risk (eg, hemophilia, von Willebrand disease, etc.)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE.;Secondary Objective: To evaluate apixaban pharmacokinetic (PK) and anti-FXa activity in pediatric subjects requiring anticoagulation for the treatment of a VTE.;Primary end point(s): Primary Safety: The composite of major and clinically relevant non-major bleeding.<br><br>Primary Efficacy: A composite of: (i) all image-confirmed and adjudicated symptomatic and asymptomatic recurrent VTE defined as either contiguous progression or non-contiguous new thrombus and including but not limited to, DVT, PE and paradoxical embolism and (ii) VTE-related mortality. <br>;Timepoint(s) of evaluation of this end point: Listed with Endpoints
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Listed with endpoints;Secondary end point(s): • All cause death <br>• VTE related mortality<br>• Index VTE status (e.g. unchanged, regression, or resolution)<br>• Stroke <br>• New or recurrent symptomatic or asymptomatic DVT .<br>• New or recurrent symptomatic or asymptomatic PE.<br>• VTEs, other than DVT or PE (i.e. cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related VTE, and splanchnic thrombosis).<br>• Major bleeding<br>• Clinically relevant non-major bleeding<br>• Minor bleeding<br>• Apixaban concentrations<br>• Anti-FXa activity