Chronic kidney disease and coagulation MedDRA version: 14.1 Level: PT Classification code 10038444 Term: Renal failure chronic System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Trade Name: Dabigatran Etexilate (pradaxa)
Product Name: Dabigatran Etexilate (pradaxa)
Pharmaceutical Form: Capsule
INN or Proposed INN: DABIGATRAN ETEXILATE
CAS Number: 211915-06-9
Current Sponsor c
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age: 18 years and older • Able and willing to give informed consent • Impaired renal function defined as a stable MDRD and/or creatinine clearance estimated using urinary excretion between 15-30 ml/min over the last 3 months before study participation • The single use of either aspirin or Vitamin K-antagonists 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 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: -Instable renal function (i.e. an increase in serum creatinine > 20% in the last three months) -Patients treated with two or more platelet aggregation inhibitors -Use of or indication for therapeutic (low molecular weight) heparin -Patients with mechanic heart valves -Any known bleeding disorder or tendency - Uncontrolled hypertension (systolic >180mmHg or diastolic >100mmHg) - Diabetes mellitus with active retinopathy - Pre-menopausal women not willing to use appropriate contraception (e.g. oral anti conceptive drugs or intrauterine devices) - Recent cerebral bleeding or cranio-cerebral trauma (within the last six months) - Moderate to severe liver impairment (ALT >2 ULN) - Gastrointestinal surgery within the last three months (except for appendectomy, cholecystectomy or herniotomy) - Use of P-glycoprotein inhibitors - Relevant acute infections (e.g. acute pneumonia) - History of allergy or hypersensitivity (including drug allergies) deemed relevant by the investigator - Planned diagnostic or therapeutic procedures with potential for uncontrollable bleeding within 30 days before, during or after the trial - Indication of past of present use of drugs or abuse - Past history of alcoholism with clinical sequelae or present use of alcohol >3U daily (male) or 2U daily (female) - Participation in another drug trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To analyze the pharmacokinetics and dynamics of Dabigatran 75 mg twice daily in patients with severe CKD (eGFR 15 - 30 ml/min) until steady state of the drug is established. ;Secondary Objective: - Effects of Dabigatran on D-dimer levels in patients with chronic kidney disease - HAS-BLED en Chads-Vasc scores;Primary end point(s): - Overall safety and tolerability profile (AEs, routine labs, vital signs) - Pharmacodynamics: onset, maximal effect, overall (AUC per 24 hrs) effect for frequently measured coagulation parameters and change from baseline when applicable (fibrinogen, AT) Hemoclot test - Pharmacokinetics: Cmax, Tmax, AUC, T½ , CL/F, Vz/F, renal excretion (tbd: plasma protein binding, proportion of total dabigatran excreted as glucuronides) ;Timepoint(s) of evaluation of this end point: Lab sampling will be drawn at the following points in time: • Predose • .5 • 1 • 2 • 3 • 4 • 6 • 8 • 12 • 23.5 • 27.5 • 47.5 • 51.5 • 71.5 • 75.5 • 95.5 • 99.5 • 119.5 • 123, 5 • 167 • 168.5 • 169 • 170 • 171 • 172 • 174 • 176 • 180 • 192 • 216 • 240 This scheme requires a patient’s admission for two days of thirteen hours (predose -13 hours and 167-180 after the first intake). From day two until day six, two samples will be drawn each day, one prior and one after oral intake of dabigatran. For all blood drawings (accept those between 0-13 and 167-180 hours), the possibility of a visiting home nurse will be offered to all study patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - D-dimer levels - HAS-BLED and Chads-Vasc scores;Timepoint(s) of evaluation of this end point: Lab sampling will be drawn at the following points in time: • Predose • .5 • 1 • 2 • 3 • 4 • 6 • 8 • 12 • 23.5 • 27.5 • 47.5 • 51.5 • 71.5 • 75.5 • 95.5 • 99.5 • 119.5 • 123, 5 • 167 • 168.5 • 169 • 170 • 171 • 172 • 174 • 176 • 180 • 192 • 216 • 240 This scheme requires a patient’s admission for two days of thirteen hours (predose -13 hours and 167-180 after the first intake). From day two until day six, two samples will be drawn each day, one prior and one after oral intake of dabigatran. For all blood drawings (accept those between 0-13 and 167-180 hours), the possibility of a visiting home nurse will be offered to all study patients. | — |
Countries
Netherlands
Contacts
Public ContactJudith Kooiman
Leiden University Medical Center
Outcome results
None listed