Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome

Nephrotic Syndrome Clinical Trial

— CAPTAIN  

Official title:

Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04850378
• Other study ID #: Prot-0824-2019
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 25, 2021
• Est. completion date: October 1, 2023

Study information

• Verified date: May 2022
• Source: University of Aarhus
• Contact: Sarah Kelddal, MD
• Phone: +45 4046 0803
• Email: sarah.kelddal[@]midt.rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Syndrome
• Thromboembolic Disease
• Thromboembolism

Intervention

Drug:
• Dalteparin
Drug: Dalteparin 200 units/kg once a day for 4-7 days.
• Apixaban
Drug: Apixaban 5 mg twice a day for 4-7 days.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initial Thrombin Generation Assay in nephrotic patients treated with Dalteparin	Thrombin Generation Assay is used to monitor the anticoagulation therapy	Predose on Day 1
Primary	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
Primary	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
Primary	Initial Thrombin Generation Assay in nephrotic patients treated with Apixaban	Thrombin Generation Assay is used to monitor the anticoagulation therapy.	Predose on Day 1
Primary	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
Primary	Steady state Thrombin Generation Assay in nephrotic patients treated with Apixaban.	Thrombin Generation Assay is used to monitor the anticoagulation therapy.	Predose day 4
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Evaluation of bleeding-events durin the study.	Number of cases with bleeding-events.	Predose until 7 days after last dose of apixaban.
Secondary	Evaluation of thromboembolic complications during the study.	Number of cases with thromboembolic complications	Predose until 7 days after last dose of apixaban.
Secondary	Comparing plasma concentration of Apixaban between group B and C	Comparing plasma-Apixaban in nephrotic patients and patients with atrial fibrillation.	Day 4
Secondary	Comparing urine concentration of Apixaban between group B and C	Comparing urine-Apixaban in nephrotic patients and patients with atrial fibrillation.	Day 4