Ignite Creation Date:
2024-05-05 @ 5:14 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00413504
Status:
COMPLETED
Last Update Posted:
2009-02-04
First Post:
2006-12-07
Brief Title:
Fondaparinux as Monotherapy for DVT andor Pulmonary Embolism
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Fondaparinux as Monotherapy for Deep Vein Thrombosis andor Pulmonary Embolism Pilot Study
Status:
COMPLETED
Status Verified Date:
2009-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine whether fondaparinux as monotherapy without warfarin is effective and safe for long-term 90 days treatment of DVT andor PE thus gaining new long-term experience and data using fondaparinux
Detailed Description:
Background and Significance
Warfarin is usually prescribed to manage long-term anticoagulation of deep vein thrombosis DVT and pulmonary embolism PE However about 5 of patients are unable to tolerate warfarin or to be safely or effectively anticoagulated Some of the reasons for discontinuing warfarin anticoagulation and switching patients to parenteral anticoagulation are as follows
1 Recurrent venous thromboembolism despite anticoagulation with warfarin
2 Clinically important bleeding complications due to warfarin
3 Inability to achieve target International Normalized Ratio INR on warfarin
4 Nonbleeding side effects of warfarin such as hair loss or rash
These patients who cannot tolerate or respond adequately to warfarin are usually managed with off-label twice-daily enoxaparin injections as monotherapy The approved duration of treatment of DVT and PE with fondaparinux is 5 to 9 days as a bridge to warfarin Until now no studies have investigated the use of fondaparinux for more than 26 days for the treatment of PE and more than 10 days for the treatment of DVT
Treatment doses of twice-daily enoxaparin are only Food and Drug Administration FDA approved for 5 to 14 days for bridging for the treatment of acute DVT andor PE patients to warfarin
Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity Its pharmacokinetic properties allow for a simple fixed-dose once daily regimen of subcutaneous injection without the need for dose adjustment based on laboratory monitoring
Fondaparinux is available only in 3 treatment doses and is prescribed once every 24 hours based on patients weight 5 mg for patients weighing less than 50 kg 75 mg for patients weighing between 50 to 100 kg and 10 mg for patients weighing more than 100 kg and is available in prefilled syringes Also fondaparinux does not cross react with heparin-induced platelet antibodies and heparin-induced thrombocytopenia has never been documented with fondaparinux
The MATISSE Investigators showed that once-daily subcutaneous administration of fondaparinux for at least 5 days and until 2 consecutive INRs were greater than 20 as a bridge to warfarin is at least as effective and safe as adjusted-dose intravenous administration of unfractionated heparin as a bridge to warfarin in the initial treatment of hemodynamically stable patients with pulmonary embolism During the 3-month follow up 42 of the 1103 patients randomly assigned to receive fondaparinux 38 percent had recurrent thromboembolic events as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin 50 percent Major bleeding occurred in 13 percent of the patients treated with fondaparinux and 11 percent of those treated with unfractionated heparin Mortality rates at three months were similar in the two groups
In another randomized double-blinded trial by the MATISSE Investigators patients were randomized to fondaparinux once daily versus enoxaparin twice daily for at least 5 days and until 2 consecutive INRs were greater than 20 as a bridge to warfarin for initial treatment of acute symptomatic DVT Fondaparinux was found to be as effective and safe as twice-daily enoxaparin during the 3-month follow up period 43 39 of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 41 of 1107 patients randomly assigned to enoxaparin Major bleeding occurred in 11 of patients receiving fondaparinux and 12 of patients receiving enoxaparin Mortality rates were 38 and 30 respectively
These two MATISSE trial totaled 4418 patients and led to the FDA approval of fondaparinux in the treatment of acute symptomatic DVT and PE as a bridge to warfarin
In this investigator-initiated trial we will conduct a cohort study with once daily fondaparinux as monotherapy without warfarin for 90-day management of DVT andor PE in patients who are unable to tolerate or respond adequately to warfarin
Research Design and Methods
This is a cohort study with a sample size of 30 patients at Brigham and Womens Hospital with history of DVT andor PE who are intolerant to warfarin or not responding to warfarin
During the study there will be 3 visits at day zero week 6 and at day 90 Patients will be monitored closely for any bleeding complications
During these visits blood will be drawn for platelet counts renal function hematocrit and transaminase level
Primary endpoints
1 Recurrent acute symptomatic DVT confirmed by venous ultrasound andor CT scan
2 Recurrent acute symptomatic PE confirmed by chest CT scan
3 Major hemorrhage defined as spinal retroperitoneal or intracranial bleeding drop in hemoglobin 2gdl or transfusion 2U or surgical or medical intervention death related to bleeding
Secondary endpoints
Comparison of Day Zero 6 week and Day 90 platelet counts renal function hematocrit and transaminase level
Drug Dose
Patients enrolled in the study will receive a weight-based dose of fondaparinux as monotherapy for 90 days for the treatment of DVT andor PE
Weight 50 kg - 5 mg daily Weight 50 - 100 kg - 75 mg daily Weight 100 kg - 10 mg daily
Biostatistical Analysis
Descriptive statistics will be performed using age gender and indication for long-term anticoagulation
Warfarin is usually prescribed to manage long-term anticoagulation of deep vein thrombosis DVT and pulmonary embolism PE However about 5 of patients are unable to tolerate warfarin or to be safely or effectively anticoagulated Some of the reasons for discontinuing warfarin anticoagulation and switching patients to parenteral anticoagulation are as follows
1 Recurrent venous thromboembolism despite anticoagulation with warfarin
2 Clinically important bleeding complications due to warfarin
3 Inability to achieve target International Normalized Ratio INR on warfarin
4 Nonbleeding side effects of warfarin such as hair loss or rash
These patients who cannot tolerate or respond adequately to warfarin are usually managed with off-label twice-daily enoxaparin injections as monotherapy The approved duration of treatment of DVT and PE with fondaparinux is 5 to 9 days as a bridge to warfarin Until now no studies have investigated the use of fondaparinux for more than 26 days for the treatment of PE and more than 10 days for the treatment of DVT
Treatment doses of twice-daily enoxaparin are only Food and Drug Administration FDA approved for 5 to 14 days for bridging for the treatment of acute DVT andor PE patients to warfarin
Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity Its pharmacokinetic properties allow for a simple fixed-dose once daily regimen of subcutaneous injection without the need for dose adjustment based on laboratory monitoring
Fondaparinux is available only in 3 treatment doses and is prescribed once every 24 hours based on patients weight 5 mg for patients weighing less than 50 kg 75 mg for patients weighing between 50 to 100 kg and 10 mg for patients weighing more than 100 kg and is available in prefilled syringes Also fondaparinux does not cross react with heparin-induced platelet antibodies and heparin-induced thrombocytopenia has never been documented with fondaparinux
The MATISSE Investigators showed that once-daily subcutaneous administration of fondaparinux for at least 5 days and until 2 consecutive INRs were greater than 20 as a bridge to warfarin is at least as effective and safe as adjusted-dose intravenous administration of unfractionated heparin as a bridge to warfarin in the initial treatment of hemodynamically stable patients with pulmonary embolism During the 3-month follow up 42 of the 1103 patients randomly assigned to receive fondaparinux 38 percent had recurrent thromboembolic events as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin 50 percent Major bleeding occurred in 13 percent of the patients treated with fondaparinux and 11 percent of those treated with unfractionated heparin Mortality rates at three months were similar in the two groups
In another randomized double-blinded trial by the MATISSE Investigators patients were randomized to fondaparinux once daily versus enoxaparin twice daily for at least 5 days and until 2 consecutive INRs were greater than 20 as a bridge to warfarin for initial treatment of acute symptomatic DVT Fondaparinux was found to be as effective and safe as twice-daily enoxaparin during the 3-month follow up period 43 39 of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 41 of 1107 patients randomly assigned to enoxaparin Major bleeding occurred in 11 of patients receiving fondaparinux and 12 of patients receiving enoxaparin Mortality rates were 38 and 30 respectively
These two MATISSE trial totaled 4418 patients and led to the FDA approval of fondaparinux in the treatment of acute symptomatic DVT and PE as a bridge to warfarin
In this investigator-initiated trial we will conduct a cohort study with once daily fondaparinux as monotherapy without warfarin for 90-day management of DVT andor PE in patients who are unable to tolerate or respond adequately to warfarin
Research Design and Methods
This is a cohort study with a sample size of 30 patients at Brigham and Womens Hospital with history of DVT andor PE who are intolerant to warfarin or not responding to warfarin
During the study there will be 3 visits at day zero week 6 and at day 90 Patients will be monitored closely for any bleeding complications
During these visits blood will be drawn for platelet counts renal function hematocrit and transaminase level
Primary endpoints
1 Recurrent acute symptomatic DVT confirmed by venous ultrasound andor CT scan
2 Recurrent acute symptomatic PE confirmed by chest CT scan
3 Major hemorrhage defined as spinal retroperitoneal or intracranial bleeding drop in hemoglobin 2gdl or transfusion 2U or surgical or medical intervention death related to bleeding
Secondary endpoints
Comparison of Day Zero 6 week and Day 90 platelet counts renal function hematocrit and transaminase level
Drug Dose
Patients enrolled in the study will receive a weight-based dose of fondaparinux as monotherapy for 90 days for the treatment of DVT andor PE
Weight 50 kg - 5 mg daily Weight 50 - 100 kg - 75 mg daily Weight 100 kg - 10 mg daily
Biostatistical Analysis
Descriptive statistics will be performed using age gender and indication for long-term anticoagulation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None