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

Overview

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.

Full Title of Study: “Assessment of Coagulation Disorders and of Enoxaparin’s Anti-Xa Activity, When Used for Thromboprophylaxis, in Severe Nephrotic Syndrome.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 30, 2018

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

  • Drug: Enoxaparin

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • Therapeutic enoxaparin’s anti-Xa activity in nephrotic syndrome.
    • Time Frame: 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.
    • Time Frame: 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 Measures

  • Severity of nephrotic syndrome.
    • Time Frame: Day 0, Day 3-5
    • Serum or/and urinary concentration of laboratory markers of disease.
  • Coagulation system protein.
    • Time Frame: Day 0, Day 3-5
    • Plasma concentration or activity of secondary hemostasis system protein (clotting factors, fibrinolysis factors, regulatory molecules).
  • Renal function.
    • Time Frame: Day 0, Day 3-5
    • Estimated glomerular filtration rate (eGFR) calculated with simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula.
  • Edema.
    • Time Frame: 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.
    • Time Frame: Day 3-5
    • Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Military Institute of Medicine, Poland
  • Provider of Information About this Clinical Study
    • Principal Investigator: Anna Matyjek, Principal Investigator – Military Institute of Medicine, Poland
  • Overall Official(s)
    • Anna Matyjek, MD, PhD, Principal Investigator, Military Institute of Medicine

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.