Intravenous Versus Subcutaneous Administration of Low Molecular Weight Heparin for Thromboprophylaxis in Critically Ill Patients

Intravenous Versus Subcutaneous Administration of Low Molecular Weight Heparin for Thromboprophylaxis in Critically Ill Patients: a Randomized Controlled Trial

Objective: To compare the pharmacokinetic profiles of intravenous versus subcutaneous route of administration of LMWH for thromboprophylaxis in critically ill patients

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Nadroparin (intravenous Infusion); Drug: Nadroparin (subcutaneous group)

Detailed Description

The study is a prospective, monocentric, randomized trial. Patients are randomized to the IV route of administration over a 4-hours infusion of nadroparin 3800 IU or to the SC route of administration. Randomization is stratified according to the need for vasopressor or not. Anti-Xa activity is measured at baseline, and at 1, 2, 4, 6, 8, 12 and 24 hours after the administration was started.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults patients > 18 years old admitted in the ICU, and for whom thromboprophylaxis is indicated

Exclusion Criteria:

• renal failure determined by glomerular filtration rate (GFR) < 30 ml/min or need for renal replacement therapy
• liver cirrhosis
• intravascular disseminated coagulation
• contra-indication to thromboprophylaxis for any reason as decided by the treating physician, or indication for therapeutic dosing anticoagulation (recent thrombo-embolic event, atrial fibrillation,…)
• patients receiving low dose of vasopressor (norepinephrine < 0.25 mcg/kg/min) to allow stratification and comparison between patients not on vasopressors and patients with a significant dose of vasopressors (norepinephrine ≥ 0.25 mcg/kg/min)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous group	Drug: Nadroparin (intravenous Infusion); Intravenous route of administration over a 4-hours infusion of nadroparin 3800 IU
Active Comparator: Subcutaneous group	Drug: Nadroparin (subcutaneous group); Subcutaneous route of administration of nadroparin 3800 IU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak anti-Xa activity	Peak anti-Xa activity obtained 4 hours after start of low molecular weight heparin administration	Peak anti-Xa activity obtained 4 hours after start of low molecular weight heparin administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough anti-Xa activity	Trough anti-Xa activity measured 24 hours after start of low molecular weight administration	Trough anti-Xa activity measured 24 hours after start of low molecular weight administration
AUC (0-24h)	Area under the curve 0-24 hours of anti-Xa activity after start of low molecular weight heparin	0-24 hours

Collaborators and Investigators

• Sponsor: Clinique Saint Pierre Ottignies

Publications and helpful links

General Publications

• De Schryver N, Serck N, Eeckhoudt S, Laterre PF, Wittebole X, Gerard L. Pharmacokinetic profiles of intravenous versus subcutaneous administration of low molecular weight heparin for thromboprophylaxis in critically ill patients: A randomized controlled trial. J Crit Care. 2022 Aug;70:154029. doi: 10.1016/j.jcrc.2022.154029. Epub 2022 Apr 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2015
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Nadroparin
• Other Study ID Numbers: IV vs SC LMWH ICU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No