Nephrotic syndrome is defined as severe proteinuria (> 3.5 g / day), edema and hypoalbuminemia. It is conditioned by a defect in the kidney's glomerular filtration barrier, resulting in the loss of a large number of plasma proteins including coagulation factors and consequently a increased risk of thromboembolic complications. The most frequent cause of nephrotic syndrome is the renal disease membranous nephropathy, which is associated with the greatest risk of thromboembolic complications. Med
Conditions
Interventions
Trade Name: Fragmin
Pharmaceutical Form: Injection
INN or Proposed INN: Dalteparin
Other descriptive name: Dalteparin
Concentration unit: IU international unit(s)
Concentration type: up to
Concentrati
Sponsors
Aarhus University Hospital, Henrik Birn
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Substudy 1: To identify abnormalities in the coagulation profile in nephrotic syndrome 60 patients will be included in substudy 1. Inclusion criteria: • Age > 18 • eGFR > 30 mL/min/1,73 m2 • P-albumin 2.2 g/day • Known glomerular disease including membranous nephropathy, which may cause nephroticy syndrom or diagnostically unresolved nephrotic syndrome with a planed kidney biopsy. Substudy 2: Up to 50 patients from substudy 1 will be treated with dalteparin to describe the effects on the biochemical coagulation profile. Inclusion criteria: • Age > 18 years • eGFR > 30 mL/min/1,73 m2 • P-albumin 2.2 g/day • Known glomerular disease including membranous nephropathy, which may cause nephroticy syndrom or diagnostically unresolved nephrotic syndrome with a planed kidney biopsy. Substudy 3: To determine the levels of plasma apixaban and its effect on the biochemical coagulation profile in nephrotic syndrome compared to atrial fibrillation patients, 10 patients with nephrotic syndrome and membranous nephropathy will be treated with apixaban and compared to 10 patients with atrial fibrillation. Patiens with nephrotic syndrome. Inclusion criteria: • Age > 18 years • eGFR > 30 mL/min/1,73 m2 • P-albumin 2.2 g/day • One of the following conditions based on a kidney biopsy: - Membranous nephropathy - Minimal change disease - Focal segmental glomerulosclerosis • Stabilized diabetes with hemoglobinA1c 18-years • eGFR > 30 mL/min/1,73 m2 • P-albumin > 36 g/lL • Stabilized diabetes with hemoglobinA1c =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Exclusion criteria: • Kontraindikation to apixaban. • Kontraindikation to dalteparin. • Known allergy or intolerance to apixaban. • Known allergy or intolerance to dalteparin. • Treatment with anticoagulation for other reasons. • Treatment with COX-1 inhibitors or ADP receptor inhibitors. • Known acquired or congenital coagulation defect not related to nephrotic syndrome or thromboembolic disease within 3 months. • Lack of compliance, comorbidity or other conditions that, in the eyes of the inclusive physician, make the patient unfit to participate in the trial. • Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study aims to describe the biochemical coagulation profile and investigate the effect of dalteparin and apixaban on this profile in patients with nephrotic syndrom. More specifically, we will: 1Identify abnormalities in the coagulation profile in nephrotic syndrom promoting a prothrombotic state. 2Describe the effects of dalteparin on the biochemical coagulation profile in nephrotic syndrom. 3Determine the levels of plasma apixaban and its effect on the biochemical coagulation profile in nephrotic syndrom compared with healthy controls. ;Secondary Objective: Not applicable;Primary end point(s): Description of the coagulation profile 1In patients with nephrotic syndrom, thromboxane B2 (marker of the primary hemostasis) as well as thrombin generation and prothrombin Fragment 1+2 (markers of the secondary hemostasis) are increased compared to healthy controls. 2In patients with nephrotic syndrom, the natural anticoagulants are decreased compared to healthy controls. 3In patients with nephrotic syndrom, clot lysis and plasminogen activator inhibitor-1 (markers of fibrinolysis) are decreased compared to healthy controls. The effects of dalteparin on the biochemical coagulation profile: 1 In patients with nephrotic syndrom, treatment with dalteparin leads to a decrease in thrombin generation compared with baseline. The effects of apixaban on the biochemical coagulation profile: 1 In patients with nephrotic syndrom, apixaban leads to a decrease in thrombin generation compared with baseline. 2 The decrease in thrombin generation following apixaban is similar in patients with nephrotic syndrom and healthy controls.;Timepoint(s) of evaluation of this end point: When the last patient is included and has completed the study, the biochemical samples will be analyzed and data will be compiled. Inclusion of patientes is expected to begin September 2020 and end in september 2023. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Apixaban: 1 The plasma and urine concentrations of apixaban in patients with nephrotic syndrom is comparable to the plasma and urine concentration of apixaban in healthy controls. 2 In patients with nephrotic syndrome the decreases in thrombin generation following dalteparin or apixaban are similar.;Timepoint(s) of evaluation of this end point: When the last patient is included and has completed the study, the biochemical samples will be analyzed and data will be compiled. Inclusion of patientes is expected to begin September 2020 and end in september 2023. | — |
Countries
Denmark
Contacts
Public ContactSarah Kelddal
Aarhus Universitets Hospital
Outcome results
None listed