Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000614
Status:
COMPLETED
Last Update Posted:
2016-03-16
First Post:
1999-10-27
Brief Title:
Prevention of Recurrent Venous Thromboembolism PREVENT
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-09
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:
A multicenter randomized double blind placebo controlled trial to determine the efficacy of long-term low dose warfarin in the secondary prevention of venous thromboembolism
Detailed Description:
BACKGROUND
Venous thromboembolism is associated with more than 300000 hospitalizations and results in thousands of deaths annually Conventional therapy consists of intravenous heparin followed by oral anticoagulants usually given for three to six months The recommended intensity of oral anticoagulants warfarin has been derived from clinical trials Such therapy is usually quite effective However some patients develop recurrent disease after the oral anticoagulants are stopped A recent randomized study evaluated the optimal duration of oral anticoagulant therapy After acute treatment with heparin subjects were treated with oral anticoagulants for either six weeks or six months with a target INR of 2 to 285 There was no difference in mortality in the two groups Recurrence was not seen while the patients were under treatment When anticoagulants were stopped recurrent thrombosis was documented in 18 percent of the patients treated for six weeks and in 95 percent of those treated for six months The period of greatest risk of recurrence for the six weeks patients was immediately after therapy was stopped There was a linear increase in cumulative risk of 5 to 6 percent per year for both treatment groups during the following 18 months
For patients who have experienced idiopathic venous thrombosis the risk of recurrence may continue even after several months of conventional therapy Further prophylactic therapy might be beneficial for the patients who are at risk for late recurrence But because of the presumed risk of bleeding and inconvenience of monitoring standard warfarin therapy most physicians usually limit treatment to three to six months
In 1997 Simioni showed a cumulative recurrence rate of VTE of 397 percent among those with factor V Leiden mutation with all recurrences occurring within three years a rate 24 times higher than among individuals without the mutation The factor V Leiden mutation is found in 4 to 6 percent of Caucasians and is the single most important cause of thromboembolism in a variety of conditions Heterozygous carriers with the mutation have VTE at a younger age than do noncarriers Among those with first VTE the prevalence of the mutation is 15 to 40 percent and among those with a family history of VTE as high as 50 percent However in a large study of men participating in the Physicians Health Study those individuals with the mutation had an increased rate of VTE over time These age-specific incidence rate differences ranged from 123 to 597 in those aged 70 or older These data suggest that confounders other than genetic predisposition are important in the development of VTE
The INR or international normalized ratio is the ratio of patient prothrombin to control prothrombin multiplied by the international sensitivity index The INR was introduced by the World Health Organization to standardize control of anticoagulant therapy internationally
DESIGN NARRATIVE
Multicenter randomized double-blind placebo-controlled A total of 253 patients were randomized to usual care plus placebo and a total of 255 patients to usual care plus a three-to-four year regimen of low-dose warfarin target INR 15 to 20 which after initial titration required infrequent outpatient monitoring Double-blind INR assessment and dose adjustment were performed every three months to ensure patient safety and to monitor compliance Primary endpoints included recurrent venous thromboembolism major bleeding episodes and all-cause mortality Separate analysis was performed of all-cause mortality in the total patient population and in those with factor V Leiden
The study consisted of 52 clinical centers a laboratory coordinating center the clinical coordinating center and the data coordinating center
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Venous thromboembolism is associated with more than 300000 hospitalizations and results in thousands of deaths annually Conventional therapy consists of intravenous heparin followed by oral anticoagulants usually given for three to six months The recommended intensity of oral anticoagulants warfarin has been derived from clinical trials Such therapy is usually quite effective However some patients develop recurrent disease after the oral anticoagulants are stopped A recent randomized study evaluated the optimal duration of oral anticoagulant therapy After acute treatment with heparin subjects were treated with oral anticoagulants for either six weeks or six months with a target INR of 2 to 285 There was no difference in mortality in the two groups Recurrence was not seen while the patients were under treatment When anticoagulants were stopped recurrent thrombosis was documented in 18 percent of the patients treated for six weeks and in 95 percent of those treated for six months The period of greatest risk of recurrence for the six weeks patients was immediately after therapy was stopped There was a linear increase in cumulative risk of 5 to 6 percent per year for both treatment groups during the following 18 months
For patients who have experienced idiopathic venous thrombosis the risk of recurrence may continue even after several months of conventional therapy Further prophylactic therapy might be beneficial for the patients who are at risk for late recurrence But because of the presumed risk of bleeding and inconvenience of monitoring standard warfarin therapy most physicians usually limit treatment to three to six months
In 1997 Simioni showed a cumulative recurrence rate of VTE of 397 percent among those with factor V Leiden mutation with all recurrences occurring within three years a rate 24 times higher than among individuals without the mutation The factor V Leiden mutation is found in 4 to 6 percent of Caucasians and is the single most important cause of thromboembolism in a variety of conditions Heterozygous carriers with the mutation have VTE at a younger age than do noncarriers Among those with first VTE the prevalence of the mutation is 15 to 40 percent and among those with a family history of VTE as high as 50 percent However in a large study of men participating in the Physicians Health Study those individuals with the mutation had an increased rate of VTE over time These age-specific incidence rate differences ranged from 123 to 597 in those aged 70 or older These data suggest that confounders other than genetic predisposition are important in the development of VTE
The INR or international normalized ratio is the ratio of patient prothrombin to control prothrombin multiplied by the international sensitivity index The INR was introduced by the World Health Organization to standardize control of anticoagulant therapy internationally
DESIGN NARRATIVE
Multicenter randomized double-blind placebo-controlled A total of 253 patients were randomized to usual care plus placebo and a total of 255 patients to usual care plus a three-to-four year regimen of low-dose warfarin target INR 15 to 20 which after initial titration required infrequent outpatient monitoring Double-blind INR assessment and dose adjustment were performed every three months to ensure patient safety and to monitor compliance Primary endpoints included recurrent venous thromboembolism major bleeding episodes and all-cause mortality Separate analysis was performed of all-cause mortality in the total patient population and in those with factor V Leiden
The study consisted of 52 clinical centers a laboratory coordinating center the clinical coordinating center and the data coordinating center
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL057951 | NIH | None | httpsreporternihgovquickSearchR01HL057951 |