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TerminatedNCT04558892ENOX-inNSUpdated Jan 30, 2023

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

A Phase 2/3 interventional study of Enoxaparin in Nephrotic Syndrome, sponsored by Military Institute od Medicine National Research Institute. Terminated at 1 site in Poland. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-01-30.

Sponsored by Military Institute od Medicine National Research Institute · Phase 2/3, Interventional, and Prevention

Why this study was terminated
The primary objectives were achieved.
Phase
Phase 2/3
Study type
Interventional
Enrollment
65
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Nephrotic Syndrome

Keywords

  • Nephrotic syndrome
  • Enoxaparin
  • Low molecular weight heparin
  • Anti-Xa activity
  • Antifactor Xa
  • Venous thromboembolism
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Prevention
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
65 participants (actual)

Study arms

  • 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

Interventions

  • DrugEnoxaparin
05

What researchers measure

Primary outcomes

  1. Therapeutic enoxaparin's anti-Xa activity in nephrotic syndrome.

    Anti-Xa activity values ≥ 0.3 IU/mL in the steady state of enoxaparin concentration, on average between days 3 and 5.

    Time frame: Average: Day 3-5

  2. Minimum threshold of enoxaparin's anti-Xa activity.

    Anti-Xa activity values ≥ 0.2 IU/mL in the steady state of enoxaparin concentration on average between days 3 and 5.

    Time frame: Average: Day 3-5

Secondary outcomes

  1. Severity of nephrotic syndrome.

    Serum or/and urinary concentration of laboratory markers of disease.

    Time frame: Day 0, Day 3-5

  2. Coagulation system protein.

    Plasma concentration or activity of secondary hemostasis system protein (clotting factors, fibrinolysis factors, regulatory molecules).

    Time frame: Day 0, Day 3-5

  3. Renal function.

    Estimated glomerular filtration rate (eGFR) calculated with simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula.

    Time frame: Day 0, Day 3-5

  4. Edema.

    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.

    Time frame: Day 0, Day 3-5

  5. Overhydration.

    Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin.

    Time frame: Day 3-5

Other outcomes

  1. Venous thromboembolic events.

    Clinically overt episode of VTE.

    Time frame: Follow-up period of 1 year from enrollment.

  2. Adverse events of enoxaparin.

    Episodes of minor and major bleeding or heparin-induced thrombocytopenia.

    Time frame: Follow-up period of 1 year from enrollment.

06

Study locations

1 site
  • Military Institute of Medicine
    Warsaw, Masovian District 04-141, Poland
07

References and documents

Publications

  • Matyjek A, Rymarz A, Nowicka Z, Literacki S, Rozmyslowicz T, Niemczyk S. Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome-A Single Center Prospective Study. J Clin Med. 2021 Dec 6;10(23):5709. doi: 10.3390/jcm10235709. PubMed 34884411 ↗
08

Registry details

Key details

Study ID
NCT04558892
Lead sponsor
Military Institute od Medicine National Research Institute
Responsible party
Anna Matyjek (Principal Investigator, Military Institute od Medicine National Research Institute) — Principal investigator
First posted
Sep 22, 2020
Start date
Oct 1, 2015
Primary completion
Nov 30, 2018
Completion
Nov 30, 2018
Last update
Jan 30, 2023

Study contacts

Anna Matyjek, MD, PhD
principal investigator · Military Institute of Medicine

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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