Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome

NCT04850378 | Completed Phase 1

• 1 other identifier: Prot-0824-2019
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrotic Syndrome; Thromboembolic Disease

Keywords

Nephrotic Syndrome; Glomerulonephritis; Hypoalbuminemia; Proteinuria; Thromboembolic Disease; Membranous Nephropathy

Outcome Measures

Primary Outcomes (12)

• 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

  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

Secondary Outcomes (4)

• Evaluation of bleeding-events durin the study.

  Predose until 7 days after last dose of apixaban.

• Evaluation of thromboembolic complications during the study.

  Predose until 7 days after last dose of apixaban.

• Comparing plasma concentration of Apixaban between group B and C

  Day 4

• Comparing urine concentration of Apixaban between group B and C

  Day 4

Study Arms (4)

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.

Drug: Dalteparin

Membranous nephropathy and nephrotic syndrome

EXPERIMENTAL

Membranous nephropathy and nephrotic syndrome.

Drug: Apixaban

Atrial fibrillation

ACTIVE COMPARATOR

Atrial fibrillation with no kidney disease.

Drug: Apixaban

Interventions

Dalteparin DRUG

Drug: Dalteparin 200 units/kg once a day for 4-7 days.

Also known as: Fragmin

Nephrotic syndrome

Apixaban DRUG

Drug: Apixaban 5 mg twice a day for 4-7 days.

Also known as: Eliquis

Atrial fibrillation; Membranous nephropathy and nephrotic syndrome

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (2)

• 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.

  PMID: 41333097 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.

  PMID: 40478760 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome; Thromboembolism; Glomerulonephritis; Hypoalbuminemia; Proteinuria; Glomerulonephritis, Membranous

Interventions

Dalteparin; apixaban

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Nephritis; Hypoproteinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Sarah Kelddal, MD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An open-label, controlled, non-randomized, interventional clinical trial.

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 20, 2021
• Study Start: March 25, 2021
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: April 11, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)