Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured

Unfractionated Heparin Treatment Clinical Trial

— DEXHEP  

Official title:

Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured in Patients Treated With Unfractionated Heparin in Different Indications-DEXHEP

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04700670
• Other study ID #: 35RC19_3001_DEXHEP
• Status: Completed
• Start date: January 16, 2020
• Est. completion date: January 16, 2021

Study information

• Verified date: January 2021
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The measurement of anti-Xa activity is classically used for the dose adjustement of unfractionated heparin (UFH) treatment and to monitor reversal of UFH by protamine during cardiac surgery with cardiopulmonary bypass (CPB). Three categories of reagents are currently available in France for the measurement of anti-Xa activity: antithrombin-containing reagents (very little used), antithrombin-free reagents and antithrombin-free reagents with dextran sulphate. Significant differences in anti-Xa results based on the reagents used were described, particularly after protamine neutralization in CPB. Indeed, dextran sulphate, contained in some reagents, could dissociate the heparin/protamine complex contributing to the higher levels of anti-Xa with these reagents. The differences observed in these patients are likely related to the presence of platelet factor 4 (PF4) in the samples from either PF4 present in vivo in patients or released in vitro after blood collection. These differences may lead to different therapeutic attitudes, including the re-administration of protamine to neutralize heparin at the end of CBP

Description:

Any hospitalized patient receiving UFH in the intensive, cardiac surgery and medicine departments of the participating centres will be offered the study by investigator. It will be included in the study after validation of the selection criteria and after collecting its non-opposition. This participation will not change the medical care of the participants.

Patients will be divided into four groups:

• Group 1: patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine.

• Group 2: patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery.

• Group 3: hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS).

Group 4: patients hospitalized in a medical non-intensive care ward.

The response to heparin treatment varies considerably depending on the clinical situation. The results found in one indication are not transposable to another indication. The 4 patient groups will provide a comprehensive response to situations in which heparin is used.

For each patient, during the usual follow-up of anti-Xa activity, and only once per patient, 3 to 4 additional blood tubes - 1 citrate tube (0.109 M) of 5 mL or 2 citrate tubes of 3 mL and 2 tubes CTAD (Citrate-Theophylline, Adenosine, Dipyrioledam) of 3 mL - will be taken during a blood test carried out in common practice. Thus, no additional invasive gestures are added by this search. CTAD contains, in addition to citrate, a platelet activation inhibitor and thus limits the in-vitro activation of platelets and thus the release of PF4.

Blood samples will be handle according to the usual procedures of each centre. All plasma will be aliquoted and stored at -80oC, until the end of inclusions in the hematology laboratories of each center.

At the end of the inclusion period, the aliquotes will be sent to the hematology laboratories of the Necker University Hospital and the University Hospital of Rennes for centralized testing.

The measurement of anti-Xa activities will be carried out on frozen-defrosted citrate and CTAD plasma with with 4 reagents:

• STA-Liquid anti-Xa (STAGO) (not containing dextran)

• Biophen Heparin LRT (Hyphen) (containing dextran)

• Berichrom (Siemens) with dextran

• Berichrom (Siemens) without dextran

The dosage of platelet factor 4 and beta-TG will be performed on frozen-defrosted plasma with CTAD with asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: January 16, 2021
• Est. primary completion date: January 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients over the age of 18;

• Hospitalized patients to receive UFH;

• No patient opposition.

Patients will be divided into four groups:

• Group 1: patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine.

• Group 2: patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery.

• Group 3: hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS).

Group 4: patients hospitalized in a medical non-intensive care ward..

Exclusion Criteria:

• pregnant or lactating women;

• adults subject to legal protection (safeguarding of justice, guardianship, guardianship), persons deprived of their liberty.

Related Conditions & MeSH terms

• Unfractionated Heparin Treatment

Intervention

Biological:
• measurement of anti-Xa activities
The measurement of anti-Xa activities will be carried out on frozen-defrosted plasma citrate and CTAD with 4 reagents STA-Liquid anti-Xa (STAGO) (not containing dextran) Biophen Heparin LRT (Hyphen) (reactive containing dextran) Berichrom (Siemens) with dextran Berichrom (Siemens) without dextran The dosage of platelet factor 4 and of the beta-TG will be carried out on frozen-defrosted plasma with the asserachrom PF4 and Asserachrom beta-TG (Diagnostica Stago) kits.

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	CHU de Dijon	Dijon
France	CH de Versailles	Le Chesnay
France	CHU de Lille	Lille
France	APHP, CHU Lariboisière	Paris
France	APHP, HOPITAL Necker enfants malades	Paris
France	Rennes University Hospital	Rennes
France	CHU de Nancy	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the effect of different reagents containing or not dextran sulphate, on the measurement of anti-Xa for different groups of patients	Measure of anti-Xa activity in CTAD plasma	5 days
Secondary	To define factors that influence the results of the biological test "anti-Xa" activity :type of anticoagulant (CTAD or citrate) .	Measure of anti-Xa activity	5 days
Secondary	To define factors that influence the results of the biological test "anti-Xa" activity :concentration of platelet factor 4 (PF4) and beta-TG present in plasma	Measure of anti-Xa activity	5 days
Secondary	To define factors that influence the results of the biological test "anti-Xa" activity :Patient characteristics including age and sex and if available, creatinine clearance, antithrombin, fibrinogen, platelet count	Measure of anti-Xa activity	5 days
Secondary	To define factors that influence the results of the biological test "anti-Xa" activity :The indication of treatment	Measure of anti-Xa activity	5 days