ENOX-inNS: Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome.

Sponsor

Military Institute of Medicine, Poland (Other)

Overall Status

Terminated

CT.gov ID

NCT04558892

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nephrotic Syndrome	Drug: Enoxaparin	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

65 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Assessment of Coagulation Disorders and of Enoxaparin's Anti-Xa Activity, When Used for Thromboprophylaxis, in Severe Nephrotic Syndrome.

Actual Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Nov 30, 2018

Actual Study Completion Date :

Nov 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nephrotic syndrome - fixed dose (NS-FD) Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.	Drug: Enoxaparin
Experimental: Nephrotic syndrome - adjusted dose (NS-AD) Drug: Enoxaparin; Dose: 1 mg/kg of ideal body weight; Administration: once daily subcutaneously.	Drug: Enoxaparin
Active Comparator: Control - fixed dose (C-FD) Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.	Drug: Enoxaparin

Arm

Intervention/Treatment

Experimental: Nephrotic syndrome - fixed dose (NS-FD)

Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.

Drug: Enoxaparin

Experimental: Nephrotic syndrome - adjusted dose (NS-AD)

Drug: Enoxaparin; Dose: 1 mg/kg of ideal body weight; Administration: once daily subcutaneously.

Drug: Enoxaparin

Active Comparator: Control - fixed dose (C-FD)

Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.

Drug: Enoxaparin

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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).
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.
Overhydration. [Day 3-5]
Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin.

Other Outcome Measures

Venous thromboembolic events. [Follow-up period of 1 year from enrollment.]
Clinically overt episode of VTE.
Adverse events of enoxaparin. [Follow-up period of 1 year from enrollment.]
Episodes of minor and major bleeding or heparin-induced thrombocytopenia.