Unfractionated Heparin TreatmentDEXHEPNCT04700670
Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured
An observational study of Unfractionated Heparin Treatment, run by Rennes University Hospital at 8 sites in France.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unfractionated Heparin Treatment
- What is being tested?
- measurement of anti-Xa activities
- How many people
- 164 participants
- Where
- 8 sitesFrance
- Study dates
- 16 Jan 2020to 16 Jan 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Any hospitalized patient receiving UFH in the intensive, cardiac surgery and medicine departments
Who may be able to join
- 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..
Who cannot join
- pregnant or lactating women;
- adults subject to legal protection (safeguarding of justice, guardianship, guardianship), persons deprived of their liberty.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
CHU Bordeaux
Bordeaux, 33604
CHU de Dijon
Dijon, 21033
CH de Versailles
Le Chesnay, 78150
CHU de Lille
Lille, 59037
APHP, CHU Lariboisière
Paris, 75010
APHP, HOPITAL Necker enfants malades
Paris, 75743
Rennes University Hospital
Rennes, 35000
CHU de Nancy
Vandœuvre-lès-Nancy, 54500
About this study
Official title: Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured in Patients Treated With Unfractionated Heparin in Different Indications-DEXHEP
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
Read the detailed 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.
- Conditions
- Unfractionated Heparin Treatment
- Being tested
- measurement of anti-Xa activities
- Keywords
- dextran sulphate, anti-Xa activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
measurement of anti-Xa activitiesBiological
Also called dosage of platelet factor 4 and of the beta-TG
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | patients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine Receives: Biological: measurement of anti-Xa activities | |
| Group 2 | patients who had cardiac surgery with CBP, between day 1 and day 5 after surgery. Receives: Biological: measurement of anti-Xa activities | |
| Group 3 | hospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS). Receives: Biological: measurement of anti-Xa activities | |
| Group 4 | patients hospitalized in a medical non-intensive care ward. Receives: Biological: measurement of anti-Xa activities |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 days
Secondary outcomes (4)
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
Measured: 5 days
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
Measured: 5 days
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
Measured: 5 days
To define factors that influence the results of the biological test "anti-Xa" activity :The indication of treatment
Measure of anti-Xa activity
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2021
- Study start16 Jan 2020
- Primary completion16 Jan 2021
- Study completion16 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unfractionated Heparin TreatmentStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Isabelle Gouin, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04700670
- Sponsor's protocol ID
- 35RC19_3001_DEXHEP
- Acronym
- DEXHEP
- Status last verified
- Jan 2021
- First submitted
- 5 Jan 2021
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lasne D, Toussaint-Hacquard M, Delassasseigne C, Bauters A, Flaujac C, Savard P, Mouton C, De Maistre E, Stepanian A, Eschwege V, Delrue M, Georges JL, Gros A, Mansour A, Leroy G, Jouffroy R, Mattei M, Beurton A, Pontis A, Neuwirth M, Nedelec-Gac F, Lecompte T, Curis E, Siguret V, Gouin-Thibault I. Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin. Thromb Haemost. 2023 Dec;123(12):1105-1115. doi: 10.1055/s-0043-1770096. Epub 2023 Jun 15.
PubMed 37321244
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Dextran Sulphate on Anti-Xa Activities Measured in Patients Treated With Unfractionated Heparin in Different Indications-DEXHEP
- ClinicalTrials.gov ID
- NCT04700670
- Acronym / sponsor ID
- DEXHEP / 35RC19_3001_DEXHEP
- Conditions
- Unfractionated Heparin Treatment
- Keywords
- dextran sulphate, anti-Xa activity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 16 Jan 2021 (actual)
- Study completion
- 16 Jan 2021 (actual)
- First posted
- 8 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Biological: measurement of anti-Xa activitiespatients with cardiac surgery with CBP. Blood samples in the operating room, 5 to 10 minutes after neutralization of heparin by protamine |
| Group 2 | – | Biological: measurement of anti-Xa activitiespatients who had cardiac surgery with CBP, between day 1 and day 5 after surgery. |
| Group 3 | – | Biological: measurement of anti-Xa activitieshospitalized patients in intensive care unit, including patients on extracorporeal life support (ECLS). |
| Group 4 | – | Biological: measurement of anti-Xa activitiespatients hospitalized in a medical non-intensive care ward. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Any hospitalized patient receiving UFH in the intensive, cardiac surgery and medicine departments
Key inclusion criteria (8 listed)
- Patients over the age of 18;
- Hospitalized patients to receive UFH;
- No patient opposition.
- 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.
Key exclusion criteria (2 listed)
- pregnant or lactating women;
- adults subject to legal protection (safeguarding of justice, guardianship, guardianship), persons deprived of their liberty.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| measurement of anti-Xa activitiesAlso: dosage of platelet factor 4 and of the beta-TGThe 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. | Biological | Group 1, Group 2, Group 3, Group 4 |
Primary outcome
Assess the effect of different reagents containing or not dextran sulphate, on the measurement of anti-Xa for different groups of patients
Time frame: 5 days
Measure of anti-Xa activity in CTAD plasma
4 secondary outcomes
To define factors that influence the results of the biological test "anti-Xa" activity :type of anticoagulant (CTAD or citrate) .
Time frame: 5 days
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
Time frame: 5 days
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
Time frame: 5 days
To define factors that influence the results of the biological test "anti-Xa" activity :The indication of treatment
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Derived from this study: PubMed 37321244Lasne D, Toussaint-Hacquard M, Delassasseigne C, Bauters A, Flaujac C, Savard P, Mouton C, De Maistre E, Stepanian A, Eschwege V, Delrue M, Georges JL, Gros A, Mansour A, Leroy G, Jouffroy R, Mattei M, Beurton A, Pontis A, Neuwirth M, Nedelec-Gac F, Lecompte T, Curis E, Siguret V, Gouin-Thibault I. Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin. Thromb Haemost. 2023 Dec;123(12):1105-1115. doi: 10.1055/s-0043-1770096. Epub 2023 Jun 15.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabelle Gouin principal investigator
Rennes University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Unfractionated Heparin Treatment, run by Rennes University Hospital at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the effect of different reagents containing or not dextran sulphate, on the measurement of anti-Xa for different groups of patients (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04700670, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.