- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06050993
Effects of Platelet Mimicking Nanoparticles in Patients With Cirrhosis (HEMCITAP)
Exploration of Primary Haemostasis in Cirrhotic Patients With T-TAS System and Effects of Platelets Mimicking Nanoparticles
Study Overview
Status
Conditions
Detailed Description
Hepatic cirrhosis is accompanied by an alteration of the haemostatic balance (primary haemostasis, coagulation, fibrinolysis). With regard to primary haemostasis, thrombocytopenia is usually moderate, due to splenic or hepatic sequestration associated with portal hypertension. Platelet synthesis is also reduced. There are also autoimmune thrombocytopenia due to the presence of anti-platelet autoantibodies. In addition, there is a thrombopathy with functional alterations in platelet adhesion and aggregation. In parallel with these abnormalities in platelet adhesion and aggregation, the quantitative increase in the level of Von Willebrand factor (VWF) preserves the capacity for platelet aggregation, even under conditions of circulating flow, despite the reduction in the intrinsic functional capacity of VWF. This increase can be explained by increased hepatic synthesis, a larger endothelial surface area in the presence of collateral circulation and repeated endothelial aggression by endotoximia during infections, as well as a decrease in clearance due to a decrease in the synthesis of ADAMTS13.
Routine investigation of abnormalities in primary haemostasis is based almost exclusively on platelet counts, as well as plasma VWF and ADAMTS13 assays. Functional platelet tests (PFA®, impedance aggregometry, light transmission aggregation) are more difficult to perform, particularly in the case of thrombocytopenia, and are not performed under circulating flow conditions. The Total Thrombus Formation Analysis System (T-TAS®01) allows analysis of haemostatic capacity in whole blood and flow conditions. Whole blood is deposited in a reservoir and then perfused onto a type I collagen-coated chip (PL chip) at a shear rate of 1500 s-1, mimicking blood flow in small arteries. As the clot forms, the pressure in the perfusion chamber increases until total occlusion occurs. The parameters measured are :
- the time required to achieve a pressure within the perfusion chamber equal to 10 kilopascal (kPa) above the baseline pressure,
- the time required to reach a pressure of 60 kPa above the base pressure in the infusion chamber (occlusion time)
- the area under the curve at 10 min. The perioperative management of cirrhotic patients leads the clinician to ask the question of prophylactic platelet transfusion in the event of thrombocytopenia of less than 30 to 50 G/L. While this threshold value is based on a low level of evidence, platelet transfusion has a poor performance in cirrhotic patients and is not without side effects. Thus, preventive platelet transfusion is not recommended. In the event of bleeding, management should consist of platelet transfusion, combined with fibrinogen and antifibrinolytic administration. Synthetic platelet mimicking particles (SPs) are made of a liposomal membrane, and "decorated" with 3 different peptides: collagen binding peptide (CBP), which binds to fibrillar collagen exposed at the subendothelium, fibrinogen mimetic peptide (FMP), which can bind to the active form of platelet integrin αIIbβ3, and VWF binding peptide (VBP), which is derived from the C2 domain of factor VIII and can bind to the D'-D3 domain of VWF.
Ex vivo, in the absence of endothelial injury, these SPs do not induce platelet aggregation in the absence of agonist but enhance aggregation in the presence of agonist. These SPs do not trigger thrombin formation on their own but in the presence of tissue factor SPs increase thrombin generation and fibrin formation. In perfusion chambers, these nanoparticles allow platelets to adhere to a collagen-coated surface and to aggregate with each other. In vivo, SPs collaborate with platelets to restore effective haemostasis in thrombocytopenic mice undergoing tail-clipping. Their haemostatic efficacy has also been demonstrated in various animal models of traumatic injury, including a mouse model of liver laceration, a porcine model of traumatic arterial haemorrhage, and a rodent model of liver resection.
The assumption of this study is that the characteristics of infusions with the T-TAS®01 system will be altered in cirrhotic patients, reflecting impairment of primary haemostasis, compared to control patients and that platelet-mimicking nanoparticles (PMNs) will correct these alterations.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
-
-
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Villejuif, France, 94800
- Anaesthesia unit of the Hepatobiliary Center - Paul Brousse Hospital
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Contact:
- Stéphanie ROULLET, MD
- Phone Number: 33 (0)1 45 59 69 49
- Email: stephanie.roullet@aphp.fr
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Contact:
- Cécile DENIS, MD
- Phone Number: 33 (0)1 49 59 56 05
- Email: cecile.denis@inserm.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adult patients who are beneficiaries of a social security scheme or beneficiaries entitled to it
- Patients followed for a cirrhotic pathology at the Paul Brousse hospital and benefiting from a scheduled anaesthesia consultation for a scheduled interventional or surgical procedure
- For non-cirrhotic patients: adult patients who are beneficiaries of a social security scheme or beneficiaries entitled to it, benefiting from a blood test scheduled as part of their usual preoperative care (patients in the hepatology or digestive surgery department operated on at the Paul Brousse hospital)
Exclusion Criteria:
- Patient not wishing to participate in the study
- Patient with a known haemostasis abnormality other than cirrhosis
- Patient on long-term antiplatelet or anticoagulant therapy
- Patient who has taken a non-steroidal anti-inflammatory drug within 5 days prior to the blood test
- Patients with thrombopathy of genetic origin
- Patient on estrogenic therapy
- Patient with cancer under treatment or treated in the last 6 months
- Patient on immunosuppressive or immunomodulatory therapy
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Cirrhotic patients
Patients known to have a cirrhosis, with an invasive procedure scheduled at the Paul Brousse hospital
|
During the preoperative procedure scheduled at the Paul Brousse hospital, 3 additional blood tubes (total volume 12 ml) will be withdrawn in addition of samplings already done for the patient's standard of care.
|
Non-cirrhotic patients
Patients without cirrhosis, with an invasive procedure scheduled at the Paul Brousse hospital
|
During the preoperative procedure scheduled at the Paul Brousse hospital, 3 additional blood tubes (total volume 12 ml) will be withdrawn in addition of samplings already done for the patient's standard of care.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the curve at 10 min of the T-TAS® 01 perfusion in PL chips
Time Frame: One day
|
One day
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time to reach a pressure of 10 kPa above baseline
Time Frame: One day
|
One day
|
Time to reach a pressure of 60 kPa above baseline
Time Frame: One day
|
One day
|
Correlations between laboratory results and perfusions' characteristics
Time Frame: Through study completion, an average of 6 months
|
Through study completion, an average of 6 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP230249
- 2023 -A00064-41 (Other Identifier: IDRCB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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