|- candidate number||3783|
|- NTR Number||NTR1392|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||4-aug-2008|
|- Secondary IDs||NL23829.068.08 |
|- Public Title||Tissue factor pathway inhibitor (TFPI) in patients with lacunar stroke|
|- Scientific Title||The role of tissue factor pathway inhibitor in the development and progression of ischemic cerebral lesions due to cerebral micro-angiopathy|
|- hypothesis||1. Is the release of TFPI by endothelium after admission of heparin different between lacunar stroke patient and healthy controls? |
2. Is the release of TFPI by endothelium after admission of heparin different between lacunar stroke patients with or without concomitant ischemic white matter lesions?
|- Healt Condition(s) or Problem(s) studied||Stroke, Stroke, Stroke, Lacunar stroke, Cerebral small vessel disease, Tissue factor pathway inhibitor (TFPI) |
|- Inclusion criteria||Patients: |
1. First ever lacunar stroke patient (>18 years old)
2. Informed consent.
3. Absent of white matter hyperintensities OR extensive white matter hyperintensities on MR-scanning of the brain.
1. Healthy controls (>18 years old)
|- Exclusion criteria||Patients:|
1. Use of oral anticoagulants, heparin (derivates) of substances with ulcerogenic action (adrenal gland hormones or anti-rheumatic medication).
2. Allergy for heparin.
3. Arterial or venous thrombosis in the past three months.
4. History of hemorrhage in urogenital tract, digestive tract or intracerebral.
5. Personal history or family history of hemorrhagic diathesis
6. Malignant hypertension
7. Brain microbleeds on Gradient-echo of FFE - images (MRI)
1. Same as patients and,
2. History of cardiovascular events (stroke, myocardial infarction or periphery artery disease)
3. Known cardiovascular risk factors (hypertension, diabetes mellitus).
|- mec approval received||no|
|- multicenter trial||no|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||1-okt-2008|
|- planned closingdate||1-jun-2009|
|- Target number of participants||30|
|- Interventions||Single intravenous dose of 7500 IU of heparin, preceded and followed by withdrawal of 30 ml of blood.|
|- Primary outcome||Levels of Tissue factor pathway inhibitor (TFPI) before and after administation of heparin in lacunar stroke patients and healthy controls.|
|- Secondary outcome||N/A|
|- Timepoints||The first sample of blood is drawn several minutes before administration of heparin. |
The second and last sample, 15 minutes after administration of heparin.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. I.L.H. Knottnerus|
|- CONTACT for SCIENTIFIC QUERIES||Drs. I.L.H. Knottnerus|
|- Sponsor/Initiator ||University Hospital Maastricht (AZM)|
(Source(s) of Monetary or Material Support)
|Dutch Thrombosis Foundation|
|- Brief summary||Endothelial dysfunction is thought to play a role in the development of silent white matter lesions (WMH) in patients with a first ever lacunar stroke. Hassan et al 1 demonstrated that several plasma markers of endothelial function were elevated in lacunar stroke patients compared to controls, but surprisingly some markers (TFPI) were lower in lacunar stroke patients with extensive WML. They concluded that this endothelial dysfunction would contribute to a pro-thrombotic state through activation of the extrinsic coagulation pathway. Earlier, we performed a pilot study in 74 patients with a first ever lacunar infarct to determine to what extent patients with lacunar stroke and concomitant WML have evidence of endothelial cell activation, and whether this would lead to activated coagulation in plasma. Patients underwent a brain MRI. WMH were graded according to the modified Fazekas scale2. vWFag, sTM and TFPI were measured using ELISA or immuno-turbidimetric assay. Chi square analysis was used to relate concentration of plasma markers (divided into tertiles) to severity of leukoaraiosis (divided into a dichotome variable). We found high levels of TFPI to be associated with extended WMH (p=0.026), but sTM and vWF were divided equal between the two groups. We concluded that higher levels of TFPI in lacunar stroke patients with extensive WML could suggest endothelial dysfunction, the lack of difference in plasma levels of vWF and sTM makes this hypothesis unlikely. In the current study, we want to further evaluate the role of TFPI (truncated and full-length) in lacunar stroke patients, by evaluating the release of TFPI by the endothelium after injection of IV heparin.|
|- Main changes (audit trail)|
|- RECORD||4-aug-2008 - 12-aug-2008|