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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.
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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Coagulation profile in Nephrotic syndrome | No Intervention | Investigation of the biochemical coagulation profile in patients with nephrotic syndrome. | |
| Nephrotic syndrome | Experimental | Nephrotic patients without diabetes. |
|
| Membranous nephropathy and nephrotic syndrome | Experimental | Membranous nephropathy and nephrotic syndrome. |
|
| Atrial fibrillation | Active Comparator | Atrial fibrillation with no kidney disease. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dalteparin | Drug | Drug: Dalteparin 200 units/kg once a day for 4-7 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Initial Thrombin Generation Assay in nephrotic patients treated with Dalteparin | Thrombin Generation Assay is used to monitor the anticoagulation therapy | Predose on Day 1 |
| Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (Nadir TGA value) | Thrombin Generation Assay is used to monitor the anticoagulation therapy | Predose day 4 |
| Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (4 hours TGA value) | Thrombin Generation Assay is used to monitor the anticoagulation therapy | 4 hours postdose on Day 4 |
| Initial Thrombin Generation Assay in nephrotic patients treated with Apixaban | Thrombin Generation Assay is used to monitor the anticoagulation therapy. | Predose on Day 1 |
| Thrombin Generation Assay in nephrotic patients treated with Apixaban over the first 24 hours. | Thrombin Generation Assay is used to monitor the anticoagulation therapy with blood samples at 2.5, 8, 24 hours. | 24 hours |
| Steady state Thrombin Generation Assay in nephrotic patients treated with Apixaban. | Thrombin Generation Assay is used to monitor the anticoagulation therapy. | Predose day 4 |
| Initial Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of bleeding-events durin the study. | Number of cases with bleeding-events. | Predose until 7 days after last dose of apixaban. |
| Evaluation of thromboembolic complications during the study. |
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Inclusion Criteria: Nephrotic patients - no intervention
Inclusion Criteria: Nephrotic patients treated with Dalteparin
Inclusion Criteria: Nephrotic patients treated with Apixaban
Inclusion Criteria: Patients with atrial fibrillation treated with Apixaban
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sarah Kelddal, MD | Aarhus University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Aarhus | 8200 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41333097 | Derived | Kelddal S, Grove EL, Duus CL, Nygaard LB, Kristensen T, Mose FH, Gregersen JW, Hvas AM, Birn H. Apixaban Concentrations and Effects on Coagulation in Patients With Nephrotic Syndrome. Kidney Med. 2025 Oct 10;7(12):101136. doi: 10.1016/j.xkme.2025.101136. eCollection 2025 Dec. | |
| 40478760 | Derived | Kelddal S, Grove EL, Duus CL, Nygaard LB, Kristensen T, Mose FH, Gregersen JW, Hvas AM, Birn H. Alterations in Coagulation and Endothelial Function in Nephrotic Syndrome: A Multicenter, Cross-Sectional Analysis. Kidney360. 2025 Nov 1;6(11):1960-1969. doi: 10.34067/KID.0000000865. Epub 2025 Jun 6. |
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| ID | Term |
|---|---|
| D009404 | Nephrotic Syndrome |
| D013923 | Thromboembolism |
| D005921 | Glomerulonephritis |
| D034141 | Hypoalbuminemia |
| D011507 | Proteinuria |
| D015433 | Glomerulonephritis, Membranous |
| ID | Term |
|---|---|
| D009401 | Nephrosis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D017985 | Dalteparin |
| C522181 | apixaban |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
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An open-label, controlled, non-randomized, interventional clinical trial.
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| Apixaban | Drug | Drug: Apixaban 5 mg twice a day for 4-7 days. |
|
|
Thrombin Generation Assay is used to monitor the anticoagulation therapy. |
| Predose on Day 1 |
| Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban over the first 24 hours. | Thrombin Generation Assay is used to monitor the anticoagulation therapy with blood samples at 2.5, 8, 24 hours. | 24 hours |
| Steady state Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban. | Thrombin Generation Assay is used to monitor the anticoagulation therapy. | Predose day 4 |
| Comparing Thrombin Generation Assay between group B and C. | Comparing Thrombin Generation Assay in nephrotic patients treated with Apixaban and patients with atrial fibrillation treated with Apixaban. | Predose, 2.5, 8, 24 hours and predose Day 4 |
| Comparing Thrombin Generation Assay between group A and C. | Comparing Thrombin Generation Assay in nephrotic patients treated with Dalteparin and patients with atrial fibrillation treated with Apixaban. | Baseline and predose Day 4 |
| Comparing Thrombin Generation Assay between group A and B. | Comparing Thrombin Generation Assay in nephrotic patients treated with Dalteparin and nephrotic patients treated with Apixaban. | Baseline and predose Day 4 |
Number of cases with thromboembolic complications
| Predose until 7 days after last dose of apixaban. |
| Comparing plasma concentration of Apixaban between group B and C | Comparing plasma-Apixaban in nephrotic patients and patients with atrial fibrillation. | Day 4 |
| Comparing urine concentration of Apixaban between group B and C | Comparing urine-Apixaban in nephrotic patients and patients with atrial fibrillation. | Day 4 |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D009393 | Nephritis |
| D007019 | Hypoproteinemia |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D002241 |
| Carbohydrates |