E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Superficial Thrombophlebitis (also known as superficial vein thrombosis) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042557 |
E.1.2 | Term | Superficial thrombophlebitis of leg |
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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 |
The primary objective of the study is to demonstrate the efficacy of fondaparinux 2.5 mg once daily versus placebo with respect to the occurrence of the primary efficacy endpoint (symptomatic VTE events and/or death) from any cause up to Day 45 (end of treatment period) in patients with isolated ST of the lower limbs. The principal safety endpoint of the study is to evaluate fondaparinux 2.5 mg once daily versus placebo with respect to the occurrence of major bleeding and/or death up to Day 49 (end of treatment period plus four days) in patients with isolated ST of the lower limbs. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to demonstrate the efficacy of fondaparinux 2.5 mg once daily versus placebo with respect to the occurrence of symptomatic VTE events and/or death from any cause up to Day 75 (end of follow-up) in patients with isolated ST of the lower limbs The principal safety endpoint will also be evaluated up to Day 75. Other safety objectives of the study are to evaluate the overall safety of fondaparinux 2.5 mg once daily versus placebo with respect to symptomatic arterial thromboembolic events and other adverse events (AE). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Fondaparinux Sodium Investigator’s Brochure. Subjects eligible for enrolment in the study must meet all the following criteria: • Hospitalised or non-hospitalised male or female patients 18 years of age or greater , • With acute symptomatic isolated ST of the lower limbs at least 5 cm long documented by standard CUS, • Able and willing to provide written informed consent. Acute ST is ST in which the delay between symptom onset and randomisation is less than three weeks. Isolated ST is ST without concomitant asymptomatic or symptomatic DVT and/or symptomatic PE. On CUS, ST will be defined as a subcutaneous non-compressible hypoechoic area in the course of an identified superficial vein (looking circular in cross sectional view, and quite rectangular in longitudinal view) of more than 5 cm in length [The STENOX Study Group, 2003] and more than 3 mm in maximum antero-posterior diameter under compression. The thrombosed vein will be named according to the anatomical nomenclature [Caggiati, 2006] and the UIP (Union Internationale de Phlébologie) consensus [Cavezzi, 2006; Coleridge, 2006]. In France, a subject will be eligible for inclusion in this study if either affiliated to or a beneficiary of a social security category. This is an additional inclusion criterion only applying to subjects enrolled in France. |
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E.4 | Principal exclusion criteria |
Exclusion criteria related to disease characteristics at presentation: • ST following sclerotherapy or resulting as a complication of an intravenous line, • Palpable hard cord without any inflammation and, on CUS, with an anteroposterior diameter < 5 mm and uniformly hyperechoic (high probability of old ST), • Delay between symptom onset and randomisation greater than 21 days, • Delay between diagnosis by CUS and randomisation greater than 48 hours (exceptionally, if the delay between CUS and randomisation exceeds this time period, the patient may be randomised if eligibility is confirmed by repeat CUS), • Treatment with antithrombotic or anticoagulant therapy, including low-dose anticoagulation, for more than 48 hours prior to randomisation, • Treatment with oral NSAIDs for more than 72 hours prior to randomisation, • Treatment with aspirin at doses greater than 325 mg per day for more than 72 hours prior to randomisation, • ST within 3 cm from the sapheno-femoral junction, • Symptomatic or asymptomatic DVT on qualifying CUS, • Documented presence of symptomatic PE, • Requirement for ligation of the sapheno-femoral junction, thrombectomy or planned intervention for stripping of varicose veins during the study period, • History of documented ST occurring within the last 90 days, • History of documented DVT or PE within the last six months, • ST in patients with active cancer (i.e. treated for cancer within the last six months). Exclusion criteria related to concomitant medication: • Anticoagulant therapy required or likely to be required during the study period (e.g. planned surgery justifying pharmacological thromboprophylaxis), • Treatment with aspirin at a dose greater than 325 mg per day or oral NSAIDs (at any dose) required or likely to be required during the study period. Exclusion criteria related to study treatments: • Known hypersensitivity to fondaparinux or its excipient, • Women of childbearing potential not using a reliable contraceptive method throughout the study period (a list of reliable contraceptive methods is provided in the accompanying SPM), • Pregnant or breast-feeding women during the study period. Exclusion criteria based on risk of bleeding: • Active, clinically significant bleeding, • Clinically significant bleeding within the past month, • Patient judged by the investigator to be at high risk of bleeding, • Major surgery within the previous three months, • Ophthalmic, spinal, and/or brain surgery within the previous twelve months, • Haemorrhagic stroke within the previous twelve months, • Severe head injury within the previous three months, • Documented congenital or acquired bleeding tendency/disorder(s), • Previous or active peptic ulcer disease, • Uncontrolled arterial hypertension (systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg), • Treatment with two or more antiplatelet agents (e.g. clopidogrel and aspirin) at any dose, • Bacterial endocarditis, • Severe hepatic impairment, • Platelet count below 100×109/L, • Prothrombin time ratio below 50%, • Calculated creatinine clearance < 30 mL/min, • Body weight < 50 kg. Other exclusion criteria related to trial methodology: • Any condition that could prevent the patient from providing written informed consent or from adhering to study treatment, • Life expectancy under three months, • Participation in any study using an investigational drug during the previous three months, • Patient in whom follow-up to Day 75 is unlikely to be feasible (e.g. patient moving to another country).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is VTE and/or death from any cause up to Day 45 (end of study treatment period). VTE is defined in this study as a composite of symptomatic PE, symptomatic DVT, symptomatic recurrence of ST or symptomatic extension of ST. |
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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 | Yes |
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 | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 124 |
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 | Information not present in EudraCT |
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 |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 14 |