Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome (CAPTAIN)

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.

Study Overview

• Status: Completed
• Conditions: Nephrotic Syndrome; Thromboembolic Disease
• Intervention / Treatment: Drug: Dalteparin; Drug: Apixaban

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).

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Coagulation profile in Nephrotic syndrome; Investigation of the biochemical coagulation profile in patients with nephrotic syndrome.
Experimental: Nephrotic syndrome; Nephrotic patients without diabetes.	Drug: Dalteparin; Drug: Dalteparin 200 units/kg once a day for 4-7 days.; Other Names: Fragmin
Experimental: Membranous nephropathy and nephrotic syndrome; Membranous nephropathy and nephrotic syndrome.	Drug: Apixaban; Drug: Apixaban 5 mg twice a day for 4-7 days.; Other Names: Eliquis
Active Comparator: Atrial fibrillation; Atrial fibrillation with no kidney disease.	Drug: Apixaban; Drug: Apixaban 5 mg twice a day for 4-7 days.; Other Names: Eliquis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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 Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Sarah Kelddal, MD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Actual): May 1, 2024
• Study Completion (Actual): May 1, 2024

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Proteinuria; Nephrotic Syndrome; Membranous Nephropathy; Glomerulonephritis; Hypoalbuminemia; Thromboembolic Disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease; Embolism and Thrombosis; Syndrome; Thromboembolism; Nephrotic Syndrome; Nephrosis; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Tinzaparin; Apixaban; Heparin, Low-Molecular-Weight; Dalteparin
• Other Study ID Numbers: Prot-0824-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No