Odiparcil For The Prevention Of Venous Thromboembolism

Study Overview
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Brief Summary
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Odiparcil is being studied to determine if it can prevent blood clots from forming after a total knee replacement and also to prove that odiparcil is safe.

Official Title
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A Dose Ranging Trial for the Evaluation of the Safety, Tolerability and Efficacy of Odiparcil in the Prevention of Venous Thromboembolism Following Total Knee Replacement Surgery

Conditions
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Deep Vein Thrombosis, Fibrillation, Atrial, Venous Thromboembolism, Pulmonary Embolism

Intervention / Treatment
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* Drug: Odiparcil
* Drug: Warfarin
* Drug: Coumadin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women must be unable to have children. Will have a total knee replacement. Exclusion Criteria: Allergic to any X-ray dye. Allergies or reactions to warfarin or coumadin. Previous VTE (venous thromboembolism) or deep vein thrombosis (DVT). On anticoagulation therapy. Renal impairment. Participated in any clinical trial in the past 30 days.

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Odiparcil|nan|
|Drug: Warfarin|nan|
|Drug: Coumadin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Total VTE Event Over 10 ± 2 Days of Treatment | Participants were assessed for VTE at all study visits and at the end of study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study did not receive a mandatory bilateral venogram following at least 8 days on study medication. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if he/ she experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or pulmonary embolism (PE) at any time during study treatment or death adjudicated to be related to VTE during study treatment. | Up to Visit 7 (10 ± 2 days of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Proximal DVT Over 10 ± 2 Days of Treatment | Proximal DVT is defined as DVT in or above the popliteal vein. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a proximal DVT if either of the ICAC answers to the questions 'Left proximal' and 'Right proximal' was 'DVT'. Percentage of participants with proximal DVT over 10 ± 2 days of treatment were reported. | Up to 12 days | 
| Percentage of Participants With Distal DVT Over 10 ± 2 Days of Treatment | A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. In both asymptomatic and symptomatic DVT, the participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'. | Up to 12 days | 
| Percentage of Participants With PE Over 10 ± 2 Days of Treatment | Participant who reported symptoms of PE were considered to have had an adjudicated objectively confirmed symptomatic PE if the ICAC answer to the question 'Was a PE identified?' was 'Yes'. E was characterized as fatal PE non-fatal PE and total PE events. Data has been presented for fatal PE non-fatal PE and total PE events over 12 days. | Up to 12 days | 
| Number of Death Due to VTE Over 10 ± 2 Days of Treatment | A participant was considered dead from an adjudicated VTE-related cause if the death classification was recorded as 'Fatal PE'. A participant was considered to have died from an investigator-assessed VTE-related cause if the investigator's death classification was recorded as 'Fatal PE'. Number of death due to VTE over 10 ± 2 days of treatment were reported. | Up to 12 days | 
| Percentage of Participants With Total Asymptomatic VTE Over 10 ± 2 Days of Treatment | A participant was included in the Independent Central Adjudication Committee (ICAC)-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic deep vein thrombosis (DVT) at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. A participant was considered to have had an asymptomatic evaluable venogram if the ICAC answer to the DVT question was 'Yes' or 'No', and to have had an adjudicated asymptomatic DVT if the answer was 'Yes'. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' is 'DVT'. | Up to 12 days | 
| Percentage of Total Symptomatic VTE Over 10 ± 2 Days of Treatment | A participant who reported symptoms of DVT was considered to had an adjudicated objectively confirmed symptomatic DVT if the ICAC answer to the question 'Was a symptomatic DVT identified?' was 'Yes' and the event happened no more than 12 days after start of study treatment (unless exemption for extended treatment was granted by the medical monitor) and no more than 1 day after end of study treatment. The participant was considered to had a proximal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. The participant was considered to had a distal DVT if either of the investigator's answers to the questions 'Left distal' and 'Right distal' was 'DVT'. Percentage of participants with total symptomatic (distal and proximal) VTE over 10 ± 2 days of treatment were reported. | Up to 12 days | 
| Concentration of Trough Anti-IIa Activity Over the Duration of Treatment and Follow-up | In all participants, additional 3 milliliter of blood was collected at the time of other blood sampling as follow: Baseline, Day 3 (predose, 2, 4, 8, 10, and 12 hours post dose), Day 5 (predose), and Day 10 (predose) or early withdrawal from study medication for the assessment of anti-factor IIa activity. Samples were collected in 3.8% sodium citrate tubes and immediately chilled in ice. Plasma were centrifuged and frozen at approximately -20ºC until time of shipment to the regional central laboratory. Concentration of Trough Anti-IIa Activity over the duration of treatment and follow-up were reported. | Up to 68 days | 
| Percentage of Participants With Major Bleeds Over 10 ± 2 Days of Treatment | A participant was included in the ICAC-adjudicated incidence of major bleeding if participant experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Major bleed was defined as clinically overt bleeding, 1) Clinical overt bleeding: clinically apparent bleeding or signs and/or symptoms suggestive of bleeding with confirmatory imaging studies (e.g., ultrasound, computed tomography) 2. Critical Site Involvement: Intracranial, retroperitoneal, intra-ocular, intraspinal, pericardial. 3. Decrease in Hgb > 2 g/dL from baseline, 4. Transfusion of > 2 units of packed RBCs, 5. Medical or Surgical Intervention for the Reported Bleed, 6. Fatal Bleed. If the event satisfied one of the above criteria. | Up to 12 days | 
| Percentage of Participants With VTE and/or Major Bleeding Over 10±2 Days of Treatment | A participant was included in the ICAC-adjudicated incidence of major bleeding if experienced an adjudicated major bleed up to 12 days after the start of study treatment and no later than 1 day after end of study treatment. Percentage of participants with VTE and/or major bleeding over 10±2 days of treatment were reported. | Up to 12 days | 
| Percentage of Participants With Total VTE Any Time After Start of Treatment | Participants were assessed for VTE at all study visits and at the end of the study (Day 10±2) or at early withdrawal. Any participant who remained asymptomatic for VTE at the end of the study were received a mandatory bilateral venogram. Participants who were withdrawn early and had been objectively confirmed to have a VTE event by a method other than venography were not required to undergo venography. A participant was included in the ICAC-adjudicated incidence of total VTE if experienced any of adjudicated asymptomatic DVT at early withdrawal or after 8-12 days of study treatment and no later than 1 day after end of study treatment, adjudicated symptomatic DVT or PE at any time during study treatment or death adjudicated to be related to VTE during study treatment. Percentage of participants with total VTE any time after start of treatment were reported. | Up to Visit 9 (Day 28 post treatment) | 
| Percentage of Participants With Elevated Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Direct Bilirubin (DB) and Total Bilirubin (TB) by 2 Fold and 3 Fold From Upper Normal Limits (ULN) Any Time On-treatment | The ranges (low concern value; high concern value) for AST (none; > 3 fold upper normal limit (ULN) ), ALT (none; >3 fold ULN), total bilirubin (none; >= 34.2 micromole per litre [umol/L]), Direct bilirubin (none; >= 34.2 umol/L). Percentage of participants with elevated values by 2 fold and 3 fold from ULN any time on-treatment were reported. | Up to 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deep vein thrombosis, total knee replacement, PE, Venous thromboembolism, DVT, pulmonary embolism, VTE