Nephrotic Syndrome, Thromboembolic Disease
Conditions
Keywords
Nephrotic Syndrome, Glomerulonephritis, Hypoalbuminemia, Proteinuria, Thromboembolic Disease, Membranous Nephropathy
Brief summary
The study aims to describe the biochemical coagulation profile and investigate the effect of Low molecular weight heparin and Apixaban on this profile in patients with nephrotic syndrome.
Detailed description
The initial part of the study is a prospective cross-sectional study which will describe the biochemical coagulation profile in nephrotic patients. It will include 60 patients with nephrotic syndrome and data from 50 anonymous blood donors matched in age and gender for comparison. The second part of the study is an open-label, controlled, non-randomized, interventional clinical trial consisting of 3 groups of patients with nephrotic syndrome or atrial fibrillation treated with either Dalteparin or Apixaban. The study participant is expected to be in stable condition after 4 full days of treatment. For administrative reasons, the final biochemical tests are performed on day 4, 5, 6 or 7 described as day 4 in this protocol. * Group A: Up to 50 patients with nephrotic syndrome treated with injection Dalteparin 200 Units/kg subcutaneous once a day for 4 days * Group B: 10 patients with nephrotic syndrome and membranous nephropathy treated with Apixaban 5 mg twice daily for 4 days. * Group C: 10 patients with atrial fibrillation and no kidney disease treated with Apixaban 5 mg twice daily for 4 days. Patients participating in the initial part of the study will be included in det second part (Group A) if they meet the inclusion criteria. If the patient is diagnosed with membranous nephropathy it is possible to be included in the initial part as well as the second part (Group A and B).
Interventions
DRUGDalteparin
Drug: Dalteparin 200 units/kg once a day for 4-7 days.
DRUGApixaban
Drug: Apixaban 5 mg twice a day for 4-7 days.
Sponsors
University of Aarhus
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An open-label, controlled, non-randomized, interventional clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Nephrotic patients - no intervention * Age 18-79 years * Estimated Glomerular Filtration Rate (eGFR) \> 49 mL/min/1.73 m2 * P-albumin \< 30 g/L * U-Albumin excretion \> 2.2 g/day * Known glomerular disease including membranous nephropathy, which may cause nephrotic syndrome or diagnostically unresolved nephrotic syndrome with a planed kidney biopsy. Inclusion Criteria: Nephrotic patients treated with Dalteparin * Age 18-79 years * eGFR \> 49 mL/min/1.73 m2 * P-albumin \< 25 g/L * U-Albumin excretion \> 2.2 g/day * Known glomerular disease including membranous nephropathy, which may cause nephrotic syndrome or diagnostically unresolved nephrotic syndrome with a planed kidney biopsy. Inclusion Criteria: Nephrotic patients treated with Apixaban * Age 18-79 years * eGFR \> 49 mL/min/1.73 m2 * P-albumin \< 25 g/L * U-Albumin excretion \> 2.2 g/day * Membranous Nephropathy Inclusion Criteria: Patients with atrial fibrillation treated with Apixaban * Age 18-79 years * eGFR \> 49 mL/min/1.73 m2 * P-albumin \> 36 g/L * U-Albumin excretion \< 300 mg/day * Atrial Fibrillation
Exclusion criteria
* Contraindication to Apixaban * Contraindication to Dalteparin * Known allergy or intolerance to Apixaban * Known allergy or intolerance to Dalteparin * Treatment with anticoagulation for other reasons. * Treatment with cyclooxygenase-1-inhibitors or Adenosine Diphosphate (ADP) receptor inhibitors. * Known acquired or congenital coagulation defect non related to nephrotic syndrome or thromboembolic disease within 3 months. * Known diabetes mellitus. * Lack of compliance, comorbidity or other conditions that, in the patients unfit to participate in the trial. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparing Thrombin Generation Assay between group A and B. | Baseline and predose Day 4 | Comparing Thrombin Generation Assay in nephrotic patients treated with Dalteparin and nephrotic patients treated with Apixaban. |
| Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban over the first 24 hours. | 24 hours | Thrombin Generation Assay is used to monitor the anticoagulation therapy with blood samples at 2.5, 8, 24 hours. |
| Steady state Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban. | Predose day 4 | Thrombin Generation Assay is used to monitor the anticoagulation therapy. |
| Comparing Thrombin Generation Assay between group B and C. | Predose, 2.5, 8, 24 hours and predose Day 4 | Comparing Thrombin Generation Assay in nephrotic patients treated with Apixaban and patients with atrial fibrillation treated with Apixaban. |
| Comparing Thrombin Generation Assay between group A and C. | Baseline and predose Day 4 | Comparing Thrombin Generation Assay in nephrotic patients treated with Dalteparin and patients with atrial fibrillation treated with Apixaban. |
| Initial Thrombin Generation Assay in nephrotic patients treated with Dalteparin | Predose on Day 1 | Thrombin Generation Assay is used to monitor the anticoagulation therapy |
| Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (Nadir TGA value) | Predose day 4 | Thrombin Generation Assay is used to monitor the anticoagulation therapy |
| Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (4 hours TGA value) | 4 hours postdose on Day 4 | Thrombin Generation Assay is used to monitor the anticoagulation therapy |
| Initial Thrombin Generation Assay in nephrotic patients treated with Apixaban | Predose on Day 1 | Thrombin Generation Assay is used to monitor the anticoagulation therapy. |
| Thrombin Generation Assay in nephrotic patients treated with Apixaban over the first 24 hours. | 24 hours | Thrombin Generation Assay is used to monitor the anticoagulation therapy with blood samples at 2.5, 8, 24 hours. |
| Steady state Thrombin Generation Assay in nephrotic patients treated with Apixaban. | Predose day 4 | Thrombin Generation Assay is used to monitor the anticoagulation therapy. |
| Initial Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban | Predose on Day 1 | Thrombin Generation Assay is used to monitor the anticoagulation therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of thromboembolic complications during the study. | Predose until 7 days after last dose of apixaban. | Number of cases with thromboembolic complications |
| Comparing plasma concentration of Apixaban between group B and C | Day 4 | Comparing plasma-Apixaban in nephrotic patients and patients with atrial fibrillation. |
| Comparing urine concentration of Apixaban between group B and C | Day 4 | Comparing urine-Apixaban in nephrotic patients and patients with atrial fibrillation. |
| Evaluation of bleeding-events durin the study. | Predose until 7 days after last dose of apixaban. | Number of cases with bleeding-events. |
Countries
Denmark
Outcome results
None listed