E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thrombosis in pediatric patients |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of shortened-duration (6 weeks total) versus conventional-duration (3 months total) anticoagulation for first-episode, provoked, acute venous thrombosis among children in whom thrombus resolution/non-occlusion (i.e. established blood flow) is evident after the initial 6 weeks of anticoagulant therapy
Hypothesis: Among children with first-episode, provoked, acute venous thrombosis in whom thrombosis is resolved or non-occlusive at six weeks follow-up, a shortened duration of anticoagulation (total six weeks; i.e. no further therapy) is non-inferior in efficacy to the conventional duration (total three months) of anticoagulation with respect to the risk of symptomatic recurrent VTE at 1 year, and is superior in safety with respect to the risk of clinically-relevant bleeding.(The hypothesis will also be tested in secondary analysis at 2 years, using the same efficacy and safety outcomes as for the 1 year primary analysis.) |
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E.2.2 | Secondary objectives of the trial |
Post-thrombotic syndrome, using Manco-Johnson Instrument |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Children (birth to <21 years of age) with radiologically-confirmed acute venous thrombosis in the past 30 days
(2) In the opinion of the investigator, the venous thrombosis was a provoked (i.e., non-spontaneous) event (e.g.: hospitalization; Central venous catheterization; infection; dehydration; surgery; trauma; immobility; use of estrogen-containing oral contraceptive pills; flare of autoimmune/rheumatologic condition). |
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E.4 | Principal exclusion criteria |
(1) prior episode of VTE;
(2) presence or history of cancer;
(3) systemic lupus erythematosus
(4) known pulmonary embolism (PE), except when limited to peripheral cavitary lesions representing septic emboli; (N.B. imaging for PE should only have been based upon clinical signs/symptoms, and is not a study procedure or requirement)
(5) Use of, or intent to use, thrombolytic therapy
(6) Patients with congenital cardiac disease involving a single or hypoplastic ventricle or otherwise requiring aintracardiac shunt
(7) Moderate/severe anticoagulant deficiency as defined by any one of the following:
a. protein C <20 IU/dL if patient is ≥3 months of age, or protein C below lower limit of detection if patient is <3 months of age;
b. antithrombin <30 IU/dL if patient is ≥3 months of age, or antithrombin below lower limit of detection if patient is <3 months of age;
c. protein S (free antigen or activity) <20 IU/dL. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PRIMARY EFFICACY: Risk of symptomatic recurrent VTE within 1 year
PRIMARY SAFETY: Risk of clinically-relevant (i.e., major plus clinically-relevant non-major [CRNM]) bleeding within 3 months (maximum randomized duration of anticoagulation) plus 10 days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visits at 6wk, 3mo, 6 mo, 1y, 2y |
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E.5.2 | Secondary end point(s) |
SECONDARY SAFETY:
1) Major bleeding episode (defined as above)
2) Minor bleeding episode (defined as all clinically-evident bleeding episodes not meeting criteria for Major or CRNM bleeding, above) within the therapy period. Nosebleeds lasting ≤ 15 minutes, bleeding from superficial lacerations, and bruising at points of minor trauma are all considered as expected events on anticoagulation, and accordingly will not be collected.
SECONDARY EFFICACY:
1) Risk of symptomatic recurrent VTE at 2 years
2) Risks of PTS at 1 year and 2 years |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visits at 6wk, 3mo, 6 mo, 1y, 2y |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Austria |
Canada |
Germany |
Israel |
Netherlands |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |