Fondaparinux in Critically Ill Patients With Renal Failure

Use of Fondaparinux in Critically Ill Patients With Renal Failure

The primary objective of this study is to determine whether a dose-adjusted prophylaxis fondaparinux regimen of 2.5 milligrams (mg) subcutaneously administered every (q) 48 hours (hr) in patients with renal failure achieves peak and trough levels similar to patients with normal renal function, and protects patients from developing venous thromboembolism (VTE). Our hypothesis is that a dose-adjusted fondaparinux regimen, which extends the dosing interval from q24 to q48 hr, in patients with estimated creatinine clearance of < 30 ml/min, will be safe and effective.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Fondaparinux

Detailed Description

We will be studying fondaparinux 2.5 mg subcutaneously every 48 hr in three distinct patient groups: 1) Acute kidney failure without hemodialysis, 2) Acute kidney failure (AKI) with intermittent hemodialysis (IHD) and 3) Acute renal failure with continuous renal replacement therapy (CRRT). All patients will be assessed for efficacy of the dose. Efficacy will be assessed by following clinically for any evidence of VTE, either deep venous thrombosis (DVT) or pulmonary embolism. In addition, lower extremity duplex studies will be performed at baseline and at the end of the study period to assess for DVT.

Secondary objectives will be safety and accumulation. Safety will be determined by assessment of clinically significant bleeding, defined as a drop in Hgb of > 2 grams (gm) in 24 hr, or the need for red blood cell transfusion related to bleeding. Accumulation may occur in renal failure and will be studied throughout the intensive care unit (ICU) stay through reevaluation of levels over time.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 89 years old
2. Body weight ≥ 50 kg or ≤ 150 kg
3. Estimated creatinine clearance of < 30 mL/min
4. Predicted ICU stay of more than 72 hours.

Exclusion Criteria:

1. Pregnant women
2. Infective Endocarditis
3. Neuraxial anesthesia or spinal puncture
4. Active bleeding
5. Treatment with vitamin K antagonists or therapeutic doses of unfractionated heparin
6. Signs of disseminated intravascular coagulation
7. Severe liver failure (serum bilirubin > 5 mg/dL)
8. Surgery planned within 24 hours of ICU admission
9. Latex allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal failure on intermittent dialysis; These are patients with renal failure, on intermittent hemodialysis (IHD), receiving fondaparinux 2.5 mg subcutaneously every 48 hours	Drug: Fondaparinux; 2.5 mg every 48 hours; Other Names: Arixtra
Experimental: Renal failure-renal replacement therapy; These are patients with renal failure, either acute or chronic, on continuous renal replacement therapy (CRRT) receiving fondaparinux 2.5 mg subcutaneously every 48 hours	Drug: Fondaparinux; 2.5 mg every 48 hours; Other Names: Arixtra
Experimental: Renal failure, not on dialysis; These are patients with acute kidney injury not yet on dialysis, receiving fondaparinux 2.5 mg subcutaneously every 48 hours	Drug: Fondaparinux; 2.5 mg every 48 hours; Other Names: Arixtra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine if an Adjusted-dose of Fondaparinux 2.5 mg Subcutaneously (SQ) q48 hr in Critically Ill Patients With Renal Failure Will Achieve Peak and Trough Levels Similar to Patients With Normal Renal Function on 2.5 mg SQ Daily Dosing of Fondaparinux.	Fondaparinux Peak Levels measured at time +3 hours after the dose, and Trough Levels, measured at time + 47 hours post-dose around the first 5 doses of fondaparinux and then every 3rd dose thereafter. Levels will be sent to our hospital laboratory and performed using a calibrated fondaparinux assay.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine Number of Participants Who Experienced a Bleeding Event, Either Major or Minor, and to Determine the Number of Participants Who Experienced a Venous Thromboembolism During the Study Period	Safety will be assessed through monitoring for clinical signs of bleeding. Major and minor bleeding will be documented. In additions, venous doppler studies of the bilateral lower extremities will be performed at study entry and study completion to monitor for any evidence of venous thromboembolism during the study period. We will report on the number of participants experiencing an adverse event during the study	2 years

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Steven D Tennenberg, MD, WSU, DMC

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 3, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimate): November 8, 2011

Study Record Updates

• Last Update Posted (Estimate): June 19, 2015
• Last Update Submitted That Met QC Criteria: June 18, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Renal Failure; Critically Ill; Fondaparinux
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Disease Attributes; Embolism and Thrombosis; Renal Insufficiency; Critical Illness; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Fondaparinux; PENTA
• Other Study ID Numbers: 112050