Venous Thromboembolism
Conditions
Keywords
Fondaparinux, Renal Failure, Critically Ill
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.
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.
Interventions
DRUGFondaparinux
2.5 mg every 48 hours
Sponsors
GlaxoSmithKline
Wayne State University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Renal Failure, on Intermittent Hemodialysis (IHD) These are patients with renal failure, on intermittent dialysis
Fondaparinux: 2.5 mg every 48 hours | 16 |
| Renal Failure, on CRRT Fondaparinux: 2.5 mg every 48 hours | 4 |
| Renal Failure, Not on Dialysis These are patients with acute kidney injury not yet on dialysis
Fondaparinux: 2.5 mg every 48 hours | 12 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Renal Failure, on Intermittent Hemodialysis (IHD) | Renal Failure, on CRRT | Renal Failure, Not on Dialysis | Total |
|---|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 16 participants | 4 participants | 12 participants | 32 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 11 Participants | 3 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 16 | 1 / 4 | 2 / 12 |
| serious Total, serious adverse events | 1 / 16 | 0 / 4 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Failure, on Intermittent Hemodialysis (IHD) | 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. | Peak Levels | 0.42 mcg/ml | Standard Deviation 0.16 |
| Renal Failure, on Intermittent Hemodialysis (IHD) | 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. | Trough Levels | 0.18 mcg/ml | Standard Deviation 0.1 |
| Renal Failure-continuous Renal Replacement Therapy | 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. | Peak Levels | 0.31 mcg/ml | Standard Deviation 0.13 |
| Renal Failure-continuous Renal Replacement Therapy | 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. | Trough Levels | 0.12 mcg/ml | Standard Deviation 0.09 |
| Renal Failure, Not on Dialysis | 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. | Peak Levels | 0.37 mcg/ml | Standard Deviation 0.21 |
| Renal Failure, Not on Dialysis | 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. | Trough Levels | 0.17 mcg/ml | Standard Deviation 0.15 |
Secondary
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
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Failure, on Intermittent Hemodialysis (IHD) | 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 | 0 participants |
| Renal Failure-continuous Renal Replacement Therapy | 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 | 0 participants |
| Renal Failure, Not on Dialysis | 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 | 0 participants |