Nephrotic Syndrome
Conditions
Keywords
Nephrotic syndrome, Enoxaparin, Low molecular weight heparin, Anti-Xa activity, Antifactor Xa, Venous thromboembolism
Brief summary
The primary objective is to test the hypothesis that enoxaparin efficacy is reduced in severe nephrotic syndrome. Another purpose is to compare two dosing regimens.
Detailed description
Nephrotic syndrome (NS) is a rare clinical condition characterized by proteinuria exceeding \>3.5 g/24h, hypoalbuminemia, dyslipidemia and edema and is associated with hypercoagulable state. In severe cases, with serum albumin ≤2.5 g/dL, the risk of venous thromboembolic events (VTE) is particularly high, and pharmacological prophylaxis is recommended. However, there is a limited evidence of its efficacy and optimal dosing. The study is designed as 3 arms clinical trial, with 2 study groups and a single control group. The study groups will include patients with severe NS parallelly, alternately assigned (1:1) into two enoxaparin dosing regimens. The control group will consisted of individuals without proteinuria and edema, similar in terms of age, anthropometric features and renal function to NS patients, who will be administered a standard enoxaparin dose. A peak anti-Xa activity at the steady state will be measured to determine the plasma concentration of enoxaparin. Additional laboratory tests for markers of NS severity, renal function and coagulation system proteins will be performed. The overhydration and body water compartments will be assessed using bioimpedance spectroscopy technique. Nephrotic patients will be followed up by 12 months to assess overt VTE and adverse events associated with enoxaparin use.
Interventions
DRUGEnoxaparin
Sponsors
Military Institute od Medicine National Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Severe NS, defined as proteinuria exceeding 3.5 g/24h or 50 mg/kg/24h and serum albumin ≤2.5 g/dL; * eGFR ≥30 mL/min/1.73 m2.
Exclusion criteria
* Body mass index (BMI) ≥40 kg/m2; * Low body mass (\<45 kg for female, \<57 kg for male); * Acute VTE; * Previously introduced anticoagulation (due to comorbidities); * Contraindications for enoxaparin; * Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic enoxaparin's anti-Xa activity in nephrotic syndrome. | Average: Day 3-5 | Anti-Xa activity values ≥ 0.3 IU/mL in the steady state of enoxaparin concentration, on average between days 3 and 5. |
| Minimum threshold of enoxaparin's anti-Xa activity. | Average: Day 3-5 | Anti-Xa activity values ≥ 0.2 IU/mL in the steady state of enoxaparin concentration on average between days 3 and 5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overhydration. | Day 3-5 | Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin. |
| Renal function. | Day 0, Day 3-5 | Estimated glomerular filtration rate (eGFR) calculated with simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula. |
| Edema. | Day 0, Day 3-5 | Clinical evaluation of edema using 3-stages scale (I: \<5 kg, II: 5-10 kg, III: \>10 kg) at enrollment and on the day of measuring anti-Xa activity of enoxaparin. |
| Severity of nephrotic syndrome. | Day 0, Day 3-5 | Serum or/and urinary concentration of laboratory markers of disease. |
| Coagulation system protein. | Day 0, Day 3-5 | Plasma concentration or activity of secondary hemostasis system protein (clotting factors, fibrinolysis factors, regulatory molecules). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events of enoxaparin. | Follow-up period of 1 year from enrollment. | Episodes of minor and major bleeding or heparin-induced thrombocytopenia. |
| Venous thromboembolic events. | Follow-up period of 1 year from enrollment. | Clinically overt episode of VTE. |
Countries
Poland
Outcome results
None listed