Clinical trial NCT04850378: Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome
Official title: Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Nephrotic Syndrome
Thromboembolic Disease
Keywords: Nephrotic Syndrome
Glomerulonephritis
Hypoalbuminemia
Proteinuria
Thromboembolic Disease
Membranous Nephropathy
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2021-04-20
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open-label, controlled, non-randomized, interventional clinical trial.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Initial Thrombin Generation Assay in nephrotic patients treated with Dalteparin
timeFrame: Predose on Day 1
measure: Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (Nadir TGA value)
timeFrame: Predose day 4
measure: Steady state Thrombin Generation Assay (TGA) in nephrotic patients treated with Dalteparin (4 hours TGA value)
timeFrame: 4 hours postdose on Day 4
measure: Initial Thrombin Generation Assay in nephrotic patients treated with Apixaban
timeFrame: Predose on Day 1
measure: Thrombin Generation Assay in nephrotic patients treated with Apixaban over the first 24 hours.
timeFrame: 24 hours
measure: Steady state Thrombin Generation Assay in nephrotic patients treated with Apixaban.
timeFrame: Predose day 4
measure: Initial Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban
timeFrame: Predose on Day 1
measure: Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban over the first 24 hours.
timeFrame: 24 hours
measure: Steady state Thrombin Generation Assay in patients with atrial fibrillation and no kidney disease treated with Apixaban.
timeFrame: Predose day 4
measure: Comparing Thrombin Generation Assay between group B and C.
timeFrame: Predose, 2.5, 8, 24 hours and predose Day 4
measure: Comparing Thrombin Generation Assay between group A and C.
timeFrame: Baseline and predose Day 4
measure: Comparing Thrombin Generation Assay between group A and B.
timeFrame: Baseline and predose Day 4
Secondary outcomes:
measure: Evaluation of bleeding-events durin the study.
timeFrame: Predose until 7 days after last dose of apixaban.
measure: Evaluation of thromboembolic complications during the study.
timeFrame: Predose until 7 days after last dose of apixaban.
measure: Comparing plasma concentration of Apixaban between group B and C
timeFrame: Day 4
measure: Comparing urine concentration of Apixaban between group B and C
timeFrame: Day 4
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Sarah Kelddal, MD
role: PRINCIPAL_INVESTIGATOR
References: