The participants enrolled in this study will all undergo major upper abdominal surgery (i.e. mostly Pylorus Preserving Pancreatico Duodenectomy or whipple procedure) mostly for pancreatic cancer, papillary carcinoma or pancreatitis. However, the indication for which the IMP is administered is intestinal ischemia and reperfusion.
Conditions
Interventions
Trade Name: Cyklokapron
Product Name: Tranexmic acid
Product Code: TA
Pharmaceutical Form: Gastroenteral solution
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo
Sponsors
Maastricht University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult patients (18 years of age and older) undergoing major upper abdominal surgery o Whipple-procedure or pylorus preserving pancreatico duodenectomy (PPPD) o Ileo-Jejunal bypass surgery o Roux-en-Y gastric bypass o Total gastrectomy o Hepatico jejunostomy o Pancreaticojejunostomy (Frey’s procedure) ? Patients who have given an informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: 150 µmol/L History of convulsions Pregnancy Known hypersensitivity of allergy for tranexamic acid Simultaneous use of thrombolytics (e.g. alteplase, streptokinase) Simultaneous use of hormonal anticonceptives or other substances that induce hemostasis. For the population who will receive doxycycline additional exclusion criteria have been formulated: Known hypersensitivity of allergy for tetracyclines. Severe liver function disorder i.e. ASAT or ALAT or AF or ?-GT >150 U/L whether or not combined with severe renal insufficiency: i.e. serum kreatinine >150 µmol/L. Severe renal insufficiency: i.e. serum kreatinine >150 µmol/L. Porphyria Myasthenia gravis Simultaneous usage (or just before or after administration of doxycycline) of oral retinoids or substances containing metalions (such as antagel or ironpreparations) Simultaneous use of methoxyflurane (anesthetic) or oral contraceptives Bodyweight beneath 50 kg History of blood coagulation disorder (inert hypocoagulation state) Pregnancy or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study aims at (further) revealing the pathophysiology of intestinal IR in man, with a specific interest for the role of proteases and protease-activated receptor-2 (PAR-2), cellular and inflammatory changes, barrier function and intestinal permeability, microscopic mucosal changes and gene expression patterns. An important element will be the determination of the effects of protease- and MMP inhibitors. By these means we hope to identify preventive and therapeutic strategies for patients with intestinal IR.;Secondary Objective: Not applicable ;Primary end point(s): The primary endpoint in this study is inflammation (neutrophil influx, complement activation, interleukins, TNF-a, COX 1-2) and protease activity in tissue as well as in blood plasma. ;Timepoint(s) of evaluation of this end point: after ischemia, after short respectively prolonged reperfusion and in control samples. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary study parameter is intestinal cell damage, which will be evaluated by assessment of plasma levels of I-FABP, ILBP as well as tissue stainings for morphology, tight junctions, apoptosis, goblet cells, mucines, cell proliferation, I-FABP, L-FABP and SM22. ;Timepoint(s) of evaluation of this end point: after ischemia, after short respectively prolonged reperfusion and in control samples. | — |
Countries
Netherlands
Contacts
Public ContactClaire Leenarts
Maastricht University
Outcome results
None listed