Fondaparinux in Critically Ill Patients With Renal Failure

• ClinicalTrials.gov Identifier: NCT01467583
• Recruitment Status: Completed
• First Posted: November 8, 2011
• Results First Posted: June 19, 2015
• Last Update Posted: June 19, 2015
• Sponsor: Wayne State University
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Steven Dov Tennenberg, MD, Wayne State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism	Drug: Fondaparinux	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Use of Fondaparinux in Critically Ill Patients With Renal Failure
• Study Start Date: November 2011
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

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 Name: 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 Name: 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 Name: Arixtra

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 2 years ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: 2 years ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Michigan

Detroit Medical Center

Detroit, Michigan, United States, 48201

Sponsors and Collaborators

Wayne State University

GlaxoSmithKline

Investigators

• Principal Investigator: Steven D Tennenberg, MD; WSU, DMC

More Information

• Responsible Party: Steven Dov Tennenberg, MD, Director, Surgical Intensive Care Unit, Wayne State University
• ClinicalTrials.gov Identifier: NCT01467583
• Other Study ID Numbers: 112050
• First Posted: November 8, 2011
• Results First Posted: June 19, 2015
• Last Update Posted: June 19, 2015
• Last Verified: June 2015

Keywords provided by Steven Dov Tennenberg, MD, Wayne State University:

Fondaparinux; Renal Failure; Critically Ill

Additional relevant MeSH terms:

Renal Insufficiency; Thromboembolism; Venous Thromboembolism; Critical Illness; Disease Attributes; Pathologic Processes; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; PENTA; Fondaparinux; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents