Ignite Creation Date:
2024-05-06 @ 4:25 PM
Last Modification Date:
2024-10-26 @ 2:10 PM
Study NCT ID:
NCT04981327
Status:
NOT_YET_RECRUITING
Last Update Posted:
2021-07-29
First Post:
2021-07-07
Brief Title:
The API-CALF Study Apixaban to Treat Calf Vein Thrombosis
Sponsor:
University Hospital Geneva
Organization:
University Hospital Geneva
Study Overview
Official Title:
The API-CALF Study Apixaban to Treat Calf Vein Thrombosis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2021-07
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:
API-CALF
Brief Summary:
Isolated distal DVT iDDVT is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment However the optimal anticoagulant intensity is uncertain and it is plausible that the best benefitrisk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses
The principal research question of the Apixaban to treat calf vein thrombosis API-CALF study is to determine whether after a conventional course of 7 days of Apixaban 10mg BID Apixaban 25mg BID experimental arm is non inferior to Apixaban 5 mg BID standard arm in preventing VTE recurrence and bleeding in patients with iDDVT Patients will be treated with Apixaban for a total of 3 months In that perspective we will conduct an international multicentre open-label assessor-blinded study
The principal research question of the Apixaban to treat calf vein thrombosis API-CALF study is to determine whether after a conventional course of 7 days of Apixaban 10mg BID Apixaban 25mg BID experimental arm is non inferior to Apixaban 5 mg BID standard arm in preventing VTE recurrence and bleeding in patients with iDDVT Patients will be treated with Apixaban for a total of 3 months In that perspective we will conduct an international multicentre open-label assessor-blinded study
Detailed Description:
Isolated distal deep vein thrombosis iDDVT is an infra-popliteal DVT without concomitant proximal DVT and without pulmonary embolism PE Until recently few large studies have focused on iDDVT and the clinical significance and therapeutic management of iDDVT was mostly based on expert opinion and gestalt rather than on strong scientific data iDDVT is the most frequent presentation of venous thromboembolic disease VTE Indeed in the large French multicentre observational OPTIMEV study where all patients with suspected DVT underwent systematic whole leg compression ultrasound CUS exploration iDDVT represented 56 of all DVTs A similar high proportion of distal DVT among DVT 521 was reported in Johnsons meta-analysis
The risk of proximal extension of iDDVT to the proximal veins is substantial In an extensive review of the literature published 15 years ago the investigators reported that the risk of proximal extension of iDDVT whether treated or left untreated ranged from 0-44 underlining the heterogeneity of the available data Data from the CALTHRO study and CACTUS trial and extrapolation of data from management studies comparing the safety of serial proximal CUS vs whole leg CUS for DVT diagnosis suggest that the rate of extension of untreated iDDVT to proximal deep veins was 10 and up to 28 in high-risk populations such as patients with cancer 3 7-9 This 10 average risk of proximal extension is far above the usual 2 cut-off for an acceptable false-negative rate for negative findings in DVT diagnostic strategies Hence from a strict natural history standpoint clinical significance of iDDVT is no longer in question In summary iDDVT is the most frequent clinical presentation of VTE and patients with iDDVT are at significant risk of proximal extension and of adverse outcomes both in the short and in the long-term
Management of iDDVT is one of the most debated issue in the field of VTE Thus in all trials that validated the use of DOAC distal location of DVT was an exclusion criterion
While the American society of Hematology ASH guidelines do not comment on iDDVT specific treatment the American college of chest physicians ACCP guidelines state that only high risk distal DVT should be systematically treated with anticoagulation Non high risk iDDVT could benefit from surveillance by repeated CUS However in the international CACTUS study the investigators observed that a primary reason for refusal of participation and failure to fulfil recruitment was that patients and their treating physicians refused that iDDVT be left untreated In routine clinical practice data from observational registries showed that the majority iDDVT are treated with full dose of anticoagulants 97 of iDDVT in the French OPTIMEV study 98 in the Italian MASTER registry and 99 in the international RIETE registry These therapeutic attitudes reflect physicians beliefs and patients preference that anticoagulation is important in case of iDDVT
For proximal DVT and PE therapeutic doses of anticoagulants are prescribed as use of lower doses was associated with an unacceptably high VTE risk In contrast for superficial vein thrombosis SVT prophylactic doses fondaparinux 25mg or rivaroxaban 10 mg daily were shown to be very effective and associated with a very low bleeding risk Regarding iDDVT risk of VTE recurrence and effectiveness of different dose regimen of anticoagulation are less clear and literature suggests that it could depend on patients characteristics Based on literature review main risk factors for VTE extensionrecurrence include cancer calf trifurcation involvement previous VTE unprovoked character of DVT or presence of a permanent risk factor and multiple vein distal vein thromboses
In the CACTUS study at 3 months the proportion of extension to proximal deep veins in the therapeutic anticoagulation arm was lower than in the placebo arm 33 vs 62 at 3 months pNS but the risk of significant bleeding was significantly higher 41 vs 003 Namely in CACTUS the benefit of therapeutic anticoagulation in terms of VTE risk reduction was offset by the excess in risk of bleeding
In summary iDDVT is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment However the optimal anticoagulant intensity is uncertain and it is plausible that the best benefitrisk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses
The principal research question of the Apixaban to treat calf vein thrombosis API-CALF study is to determine whether after a conventional course of 7 days of Apixaban 10mg BID Apixaban 25mg BID experimental arm is non inferior to Apixaban 5 mg BID standard arm in preventing VTE recurrence and bleeding in patients with iDDVT Patients will be treated with Apixaban for a total of 3 months In that perspective we will conduct an international multicentre open-label assessor-blinded study
The risk of proximal extension of iDDVT to the proximal veins is substantial In an extensive review of the literature published 15 years ago the investigators reported that the risk of proximal extension of iDDVT whether treated or left untreated ranged from 0-44 underlining the heterogeneity of the available data Data from the CALTHRO study and CACTUS trial and extrapolation of data from management studies comparing the safety of serial proximal CUS vs whole leg CUS for DVT diagnosis suggest that the rate of extension of untreated iDDVT to proximal deep veins was 10 and up to 28 in high-risk populations such as patients with cancer 3 7-9 This 10 average risk of proximal extension is far above the usual 2 cut-off for an acceptable false-negative rate for negative findings in DVT diagnostic strategies Hence from a strict natural history standpoint clinical significance of iDDVT is no longer in question In summary iDDVT is the most frequent clinical presentation of VTE and patients with iDDVT are at significant risk of proximal extension and of adverse outcomes both in the short and in the long-term
Management of iDDVT is one of the most debated issue in the field of VTE Thus in all trials that validated the use of DOAC distal location of DVT was an exclusion criterion
While the American society of Hematology ASH guidelines do not comment on iDDVT specific treatment the American college of chest physicians ACCP guidelines state that only high risk distal DVT should be systematically treated with anticoagulation Non high risk iDDVT could benefit from surveillance by repeated CUS However in the international CACTUS study the investigators observed that a primary reason for refusal of participation and failure to fulfil recruitment was that patients and their treating physicians refused that iDDVT be left untreated In routine clinical practice data from observational registries showed that the majority iDDVT are treated with full dose of anticoagulants 97 of iDDVT in the French OPTIMEV study 98 in the Italian MASTER registry and 99 in the international RIETE registry These therapeutic attitudes reflect physicians beliefs and patients preference that anticoagulation is important in case of iDDVT
For proximal DVT and PE therapeutic doses of anticoagulants are prescribed as use of lower doses was associated with an unacceptably high VTE risk In contrast for superficial vein thrombosis SVT prophylactic doses fondaparinux 25mg or rivaroxaban 10 mg daily were shown to be very effective and associated with a very low bleeding risk Regarding iDDVT risk of VTE recurrence and effectiveness of different dose regimen of anticoagulation are less clear and literature suggests that it could depend on patients characteristics Based on literature review main risk factors for VTE extensionrecurrence include cancer calf trifurcation involvement previous VTE unprovoked character of DVT or presence of a permanent risk factor and multiple vein distal vein thromboses
In the CACTUS study at 3 months the proportion of extension to proximal deep veins in the therapeutic anticoagulation arm was lower than in the placebo arm 33 vs 62 at 3 months pNS but the risk of significant bleeding was significantly higher 41 vs 003 Namely in CACTUS the benefit of therapeutic anticoagulation in terms of VTE risk reduction was offset by the excess in risk of bleeding
In summary iDDVT is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment However the optimal anticoagulant intensity is uncertain and it is plausible that the best benefitrisk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses
The principal research question of the Apixaban to treat calf vein thrombosis API-CALF study is to determine whether after a conventional course of 7 days of Apixaban 10mg BID Apixaban 25mg BID experimental arm is non inferior to Apixaban 5 mg BID standard arm in preventing VTE recurrence and bleeding in patients with iDDVT Patients will be treated with Apixaban for a total of 3 months In that perspective we will conduct an international multicentre open-label assessor-blinded study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None