| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The subjects who will partcipate to this clinical trial are acutely ill medical patients with restricted mobility. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049909 |
| E.1.2 | Term | Venous thromboembolism prophylaxis |
|
| 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 compare the efficacy of once daily (q.d.) subcutaneous (s.c.) injections of 20 mg AVE5026 (10 mg in patients with severe renal insufficiency [SRI]) with q.d. s.c. injections of 40 mg enoxaparin (20 mg in patients with SRI) administered during 10-14 days for the primary prevention of venous thromboembolic events (VTE) in patients hospitalized for acute medical illness. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety of AVE5026 in patients hospitalized for acute medical illness, and to document AVE5026 exposures in this population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient with an acute medical condition requiring bed rest for at least 3 days
2. Age ≥40 years
3. Hospitalized for at least one of the following medical conditions:
- Congestive heart failure (NYHA class III/IV)
- Acute respiratory failure (not requiring mechanical ventilation)
- Acute infection (without septic shock)*
- Acute rheumatic disorder*
- Acute episode of inflammatory bowel disease*
* Patients with these conditions should have at least one additional risk factor for VTE.
4. Signed written informed consent
|
|
| E.4 | Principal exclusion criteria |
Exclusion criteria related to study methodology:
1. Previous surgery with general anesthesia within 30 days before inclusion
2. Any major surgery planned during the investigational treatment period
3. Any treatment with other antithrombotic agents within 2 weeks prior to randomization or planned during the course of the study, such as:
- Parenteral anticoagulants (UFH, LMWH [i.e. enoxaparin, dalteparin, nadroparin,..], fondaparinux, bivalirudin, hirudin)
*Note: A patient may be included if thromboprophylaxis has been initiated with a single dose of UFH or LMWH administered at least 12 hours before randomization.
- Oral anticoagulants (vitamin K antagonists)
- GPIIb/IIIa antagonists: abciximab, eptifibatide, tirofiban
- Thrombolytic agents
*Note: Chronic treatment with antiplatelet agents such as low-dose aspirin (up to 325 mg/day), clopidogrel or ticlopidine in patients with coronary artery disease is allowed.
4. Subject who requires a curative anticoagulant or thrombolytic treatment
5. Acute stroke
6. Subject unlikely to comply with the protocol, e.g. uncooperative attitude, inability to give informed consent, return for follow-up visits, inability to receive daily injection (by a health care professional) after hospital discharge and unlikelihood of completing the study
7. Treatment with any investigational product or investigational device in the last 30 days or 5 half lives (if relevant) prior to randomization
8. Any previous exposure to AVE5026 (e.g. participation in any previous AVE5026 clinical trial).
9. Anticipated survival <6 months
Note: A patient may not be enrolled in the study more than once (i.e. randomized more than once).
Exclusion criteria related to enoxaparin:
10. Active major bleeding
11. Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of enoxaparin sodium
12. Known hypersensitivity to enoxaparin sodium (e.g. pruritus, urticaria, anaphylactoid reactions)
13. Known hypersensitivity to heparin or pork products
14. Conditions with increased risk of hemorrhage, such as bacterial endocarditis, congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophtalmological surgery
Exclusion criteria related to AVE5026
15. End stage renal disease (estimated creatinine clearance <10 mL/min) or patients on dialysis
16. Pregnant or breast-feeding women
17. Women of childbearing potential not protected by highly effective contraceptive method of birth control as defined for contraception in the Informed Consent Form for the duration of the study and/or who are unwilling or unable to be tested for pregnancy
*Note: Pregnancy status should be checked by serum or urine pregnancy testing prior to exposure to the investigational product. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is a composite of the following VTE outcome events recorded up to Day 15 or up to the day of the mandatory CUS (Day 10 - Day 15), whichever comes first, and confirmed by a blinded Adjudication Committee:
• Any asymptomatic proximal DVT detected by CUS
• Confirmed DVT and/or non-fatal pulmonary embolism (PE) in case of symtoms earlier than the date of the mandatory CUS
• Any VTE-related deaths (fatal PE or unexplained deaths)
Mandatory CUS should be performed within one calendar day of last dosing.
For symptomatic events an adjudication dossier containing relevant documentation such as all relevant films, (venography or CUS for DVT, ventilation/perfusion lung scan, pulmonary angiogram or spiral CT lung scan for PE, or autopsy report if available) will be provided for adjudication.
Other endpoints:
• Each component of the primary efficacy endpoint up to Day 15 or up to the day of the mandatory CUS (whichever comes first)
• Initiation of curative treatment by the investigator after local VTE assessment
Safety parameters include major bleeding, clinically relevant non-major bleeding (adjudicated by a blinded Adjudication Committee), transfusions requirement, hemoglobin, platelet count, liver and renal laboratory data, (S)AEs and all-cause deaths (classified as VTE-related death, fatal bleeding or other by a blinded Adjudication Committee) up to 3 calendar days after last IP injection and up to
Day 42.
Pharmacokinetics:
Four blood samples per patient will be drawn in all patients from selected centers to document the AVE5026 exposures in this population. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 246 |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| 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 months | 33 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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