Ignite Creation Date:
2024-05-06 @ 11:04 AM
Last Modification Date:
2024-10-26 @ 12:40 PM
Study NCT ID:
NCT03426982
Status:
UNKNOWN
Last Update Posted:
2018-03-14
First Post:
2018-02-01
Brief Title:
Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
Sponsor:
Wuhan Asia Heart Hospital
Organization:
Wuhan Asia Heart Hospital
Study Overview
Official Title:
A Randomized Study Aimed at Comparing Activated Partial Thromboplastin Time and Anti-Xa Activity and in Patients Requiring Unfractionated Heparin Infusion
Status:
UNKNOWN
Status Verified Date:
2018-03
Last Known Status:
RECRUITING
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:
CATCH
Brief Summary:
Background
Unfractionated heparin UFH is a sulfated polysaccharide extracted from porcine intestinal mucosa that enhances the inhibitory activity of the natural anticoagulant antithrombin towards most activated clotting factors F particularly FXa and FIIa thrombin Despite the growing interest for low molecular weight derivatives LMWH UFH is still widely used for different indications including the treatment of acute thrombosis including venous thromboembolism coronary syndromes ACS and other thrombotic diseases UFH is administered by parenteral route either intravenous IV or sub-cutaneous SCActually there is evidence that the risk of recurrence of thrombosis is increased when heparin levels fells below the lower limit of the therapeutic range while the hemorrhagic risk increases with heparin levels above the upper limit of the therapeutic range Moreover the anticoagulant response to UFH is highly variable for one individual to another As the clinical efficacy of heparin is dependent on maintaining an anticoagulant effect above a minimum level careful laboratory monitoring of UFH treatment is mandatory For that purpose two options are offered to the clinicians i to evaluate either the prolongation of a global clotting assay the activated partial thromboplastin time aPTT and ii to measure the heparin-enhanced inhibitory activity of AT toward purified activated factors such as FIIa and FXa using chromogenic substrate-based assays UFH therapy is still widely monitored by the aPTT a global clotting assay that reflects the ability of heparin to enhance the inhibitory activity of AT against FIIa FXa and other activated factors The therapeutic range of aPTT prolongation is highly dependent on the reagent and analyzer used As the consequence it must be defined by each laboratory in its own technical conditions for each reagent batch to correlate with heparin levels between 020 and 040 UmL protamine sulfate titration corresponding to anti-FXa activity between 030 and 070 IUmL In that connection the prolongation of aPTT corresponding to antiFXa activity between 030 - 070 IUmL is highly variable depending of the reagents egbetween 16 - 27 x control for weakly sensitive reagents and between 37 - 62 x control for highly sensitive reagents The use of aPTT has advantages as it is easy-to-perform quick inexpensive but faces numerous challenges due to the significant influence of the technical conditions reagentinstrument on the test result to lot-lot variation in reagent sensitivity to the need of studies to evaluate the therapeutic range to limited therapeutic range and also to non-specific prolongation in the case of lupus anticoagulant factors deficiency inhibitors or shortening in the case of high factor levels particularly FVIIIIn contrast the use of chromogenic anti-Xa assays has many advantages particularly a published therapeutic range for UFH ie between 030 and 070 IUmL a specificity to its interaction with AT no Heparin Cofactor II interference by using bovine FIIa or short incubation time and faces few challenges such as limited availability in some area and a cost that is slightly higher than that of aPTT In addition anti-Xa assays allow accurate measurement of all heparins derivatives and particularly LMWHs and fondaparinux
Since the first reports in the mid-eighties some small sized studies have compared the two monitoring strategies mainly retrospectively designed 7-11 Even though one single prospective randomized management study evaluated the comparison between the two monitoring strategies with clinical end-points ie recurrence of thrombosis and bleeding complication in a cohort of 131 patients with VTE All concluded to a trend toward higher or at least similar safetyefficacyefficiency when patients were monitored using antiXa activity vs aPTT Even though differences were not significant due to the lack of power of these studies
Unfractionated heparin UFH is a sulfated polysaccharide extracted from porcine intestinal mucosa that enhances the inhibitory activity of the natural anticoagulant antithrombin towards most activated clotting factors F particularly FXa and FIIa thrombin Despite the growing interest for low molecular weight derivatives LMWH UFH is still widely used for different indications including the treatment of acute thrombosis including venous thromboembolism coronary syndromes ACS and other thrombotic diseases UFH is administered by parenteral route either intravenous IV or sub-cutaneous SCActually there is evidence that the risk of recurrence of thrombosis is increased when heparin levels fells below the lower limit of the therapeutic range while the hemorrhagic risk increases with heparin levels above the upper limit of the therapeutic range Moreover the anticoagulant response to UFH is highly variable for one individual to another As the clinical efficacy of heparin is dependent on maintaining an anticoagulant effect above a minimum level careful laboratory monitoring of UFH treatment is mandatory For that purpose two options are offered to the clinicians i to evaluate either the prolongation of a global clotting assay the activated partial thromboplastin time aPTT and ii to measure the heparin-enhanced inhibitory activity of AT toward purified activated factors such as FIIa and FXa using chromogenic substrate-based assays UFH therapy is still widely monitored by the aPTT a global clotting assay that reflects the ability of heparin to enhance the inhibitory activity of AT against FIIa FXa and other activated factors The therapeutic range of aPTT prolongation is highly dependent on the reagent and analyzer used As the consequence it must be defined by each laboratory in its own technical conditions for each reagent batch to correlate with heparin levels between 020 and 040 UmL protamine sulfate titration corresponding to anti-FXa activity between 030 and 070 IUmL In that connection the prolongation of aPTT corresponding to antiFXa activity between 030 - 070 IUmL is highly variable depending of the reagents egbetween 16 - 27 x control for weakly sensitive reagents and between 37 - 62 x control for highly sensitive reagents The use of aPTT has advantages as it is easy-to-perform quick inexpensive but faces numerous challenges due to the significant influence of the technical conditions reagentinstrument on the test result to lot-lot variation in reagent sensitivity to the need of studies to evaluate the therapeutic range to limited therapeutic range and also to non-specific prolongation in the case of lupus anticoagulant factors deficiency inhibitors or shortening in the case of high factor levels particularly FVIIIIn contrast the use of chromogenic anti-Xa assays has many advantages particularly a published therapeutic range for UFH ie between 030 and 070 IUmL a specificity to its interaction with AT no Heparin Cofactor II interference by using bovine FIIa or short incubation time and faces few challenges such as limited availability in some area and a cost that is slightly higher than that of aPTT In addition anti-Xa assays allow accurate measurement of all heparins derivatives and particularly LMWHs and fondaparinux
Since the first reports in the mid-eighties some small sized studies have compared the two monitoring strategies mainly retrospectively designed 7-11 Even though one single prospective randomized management study evaluated the comparison between the two monitoring strategies with clinical end-points ie recurrence of thrombosis and bleeding complication in a cohort of 131 patients with VTE All concluded to a trend toward higher or at least similar safetyefficacyefficiency when patients were monitored using antiXa activity vs aPTT Even though differences were not significant due to the lack of power of these studies
Detailed Description:
Aim of the study Based on available data a randomized trial aimed at comparing the efficacy and safety of monitoring UFH treatments using aPTT and anti-FXa activity in patients treated with fulldoses of UFH could validly be carried out
Study design
Primary objectives safety and efficacy
Secondary objectives efficiency and cost effectiveness
Primary evaluation criteria bleeding complications n and thrombotic complications
Secondary evaluation criteria percentage of test results within the therapeutic rangenumber of tests perfomed per day number of daily dose adjustments total dosage of heparin given to the patients mean time to achieve therapeutic anticoagulation transfusion rates health economics analysis total treatment cost
Calculation of number of patients to be evaluated
According to the only randomized study published to date A the bleeding rate was 15 n165 in the group of patients monitored using Anti-FXa activity vs 61 n466 in theaPTT group The difference was not significant p036 due to the lack of power of the study n131 patients Taking into account these bleeding risks and 005 as the alpha risk and 020 005 as the beta risk the number of patients to be included would be 323 506 in each treatment arm
Description of the two monitoring strategies
Patients should be randomized to be monitored using either
Anti-Xa activity heparin levels with the therapeutic range between 030 and 070IUmL corresponding to 02 to 04 protamine sulfate titration assay 3
aPTT wIth the usual therapeutic range of 15 to 25 fold the control time which was the usually used therapeutic range in the institution
Example of nomogram for heparin dose-adjustment when monitored using aPTT or anti-Xa activity 12Practical considerations
Mechanism of randomization electronic
After randomization the patients must be monitored using either anti-Xa activity or aPTT
Only that specific test should be prescribed by the ward and only that the corresponding test result be given by the laboratory
Ideally fresh patients samples should be evaluated for both Anti-Xa activity and aPTT data being recorded but only the prescribed test should be given to the ward In addition it would be necessary to store aliquots 05-10 mL each of plasmas samples frozen at -70C for control purpose
Patients must be follow-up at 3-months
Data to be collected
Patients demographical data sex age indication of UFH therapy VTE ACS othercomorbidity cancer pregnancy postoperative period other concomitant therapy medication such as oral contraceptive previous history of thrombosis DVT ACSstroke other Duration in hours and total dosage IU of heparin therapy before randomization if any Route of administration IV SC daily heparin dosage IU duration of treatment time to achieve therapeutic range number of dosage change per day laboratory test results anti-Xa activity or aPTT Outcome death any cause to be recorded description of any bleeding complication when localization classification as major or minor or recurrence of thrombosis whenlocalization while on UFH therapy and within the 3-month follow-up
Study design
Primary objectives safety and efficacy
Secondary objectives efficiency and cost effectiveness
Primary evaluation criteria bleeding complications n and thrombotic complications
Secondary evaluation criteria percentage of test results within the therapeutic rangenumber of tests perfomed per day number of daily dose adjustments total dosage of heparin given to the patients mean time to achieve therapeutic anticoagulation transfusion rates health economics analysis total treatment cost
Calculation of number of patients to be evaluated
According to the only randomized study published to date A the bleeding rate was 15 n165 in the group of patients monitored using Anti-FXa activity vs 61 n466 in theaPTT group The difference was not significant p036 due to the lack of power of the study n131 patients Taking into account these bleeding risks and 005 as the alpha risk and 020 005 as the beta risk the number of patients to be included would be 323 506 in each treatment arm
Description of the two monitoring strategies
Patients should be randomized to be monitored using either
Anti-Xa activity heparin levels with the therapeutic range between 030 and 070IUmL corresponding to 02 to 04 protamine sulfate titration assay 3
aPTT wIth the usual therapeutic range of 15 to 25 fold the control time which was the usually used therapeutic range in the institution
Example of nomogram for heparin dose-adjustment when monitored using aPTT or anti-Xa activity 12Practical considerations
Mechanism of randomization electronic
After randomization the patients must be monitored using either anti-Xa activity or aPTT
Only that specific test should be prescribed by the ward and only that the corresponding test result be given by the laboratory
Ideally fresh patients samples should be evaluated for both Anti-Xa activity and aPTT data being recorded but only the prescribed test should be given to the ward In addition it would be necessary to store aliquots 05-10 mL each of plasmas samples frozen at -70C for control purpose
Patients must be follow-up at 3-months
Data to be collected
Patients demographical data sex age indication of UFH therapy VTE ACS othercomorbidity cancer pregnancy postoperative period other concomitant therapy medication such as oral contraceptive previous history of thrombosis DVT ACSstroke other Duration in hours and total dosage IU of heparin therapy before randomization if any Route of administration IV SC daily heparin dosage IU duration of treatment time to achieve therapeutic range number of dosage change per day laboratory test results anti-Xa activity or aPTT Outcome death any cause to be recorded description of any bleeding complication when localization classification as major or minor or recurrence of thrombosis whenlocalization while on UFH therapy and within the 3-month follow-up
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