Clinical trial NCT02970032
Conditions: Deep-Venous Thrombosis Pulmonary Embolism Venous Thromboembolism
Sponsor: University of Utah
Start date: 2016-11-10; Completion date: 2017-12-08
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to determine if fixed dose heparin infusions at a rate of 500 units/hour are sufficient to maintain a target anti-Xa of 0.1-0.35 IU/mL for venous thromboembolism (VTE) prophylaxis in patients undergoing microvascular surgery. Additionally, a pilot protocol has been developed to titrate these heparin infusions to ensure patients have sufficient VTE prophylaxis. All patients will be enrolled in the observational arm of the study and receive anti-Xa level monitoring. Patients with out-of-range anti-Xa levels will cross over to the interventional arm of the study and receive real time heparin infusion dose adjustments per the pilot protocol. The primary outcome measured will be the percentage of patients with anti-Xa levels in the target range of 0.1-0.35 IU/mL while on a heparin infusion at 500 units/hour.

Detailed description:

Arms: arm 1: The investigators will identify surgical patients placed on fixed dose heparin infusions at their attending surgeon's discretion-the proposed research will not dictate the initiation of the heparin drip intraoperatively. However, the investigators will identify patients already on heparin, evaluate steady state heparin anti-Xa levels and adjust patient's dose if necessary based on steady state anti-Xa levels. Eligible patients will be started on heparin fixed-dose intraoperatively. Steady state anti-Xa levels will be drawn at least 6 hours after initiation of heparin infusion. Goal anti-Xa levels will be 0.1-0.35 IU/mL. arm 2: Patients with identified out of range levels will receive pharmacist-driven real time heparin dose adjustment and will receive follow-up steady state anti-Xa levels. Anti-Xa level monitoring will be discontinued when in range peak levels are obtained, when heparin infusions are discontinued at surgeon discretion, or when the patient is discharged.
Interventions: intervention 1: Real time heparin dose adjustment intervention 2: Standard heparin dose
Intervention descriptions: intervention 1: Patients will have steady state anti-Xa levels drawn at least 6 hours after initiation of heparin infusion. Patients with out of range anti-Xa levels will receive real time heparin dose adjustment followed by repeat anti-Xa levels. intervention 2: Patients will be placed on heparin infusions per their surgeon's discretion.

Protocol documents:
Prot_SAP_000.pdf: 
Protocol Summary 
Version: August 24, 2016 
 
Evaluation of anti-Xa levels in surgery patients receiving fixed dose heparin 
University of Utah IRB_00095514  
NCT02970032 
  
OBJECTIVES:   
The aims of this study are to:  
- 
Determine if fixed dose heparin infusions at a rate of 500 units/hour are sufficient to maintain a 
target anti-Xa of 0.1-0.35 IU/mL for VTE prophylaxis in patients undergoing microsurgical 
procedures.   
- 
Develop and implement a pilot protocol to titrate heparin drips initiated at 500 units/hour 
following microsurgical procedures to ensure patients have sufficient VTE prophylaxis.  
  
Hypothesis: Fixed dose heparin drips at 500 units/hour are not sufficient to maintain the target anti-Xa 
of 0.1-0.35 IU/mL for VTE prophylaxis in all patients undergoing microsurgical procedures.   
  
PARTICIPANT SELECTION CRITERIA:  
Inclusion Criteria:   
- 
Patients undergoing microsurgical procedures at the University of Utah Hospital  Initiation of a 
heparin infusion at a rate of 500 units/hour postoperatively   
  
Exclusion Criteria:   
- 
Age <18 years old  
- 
Pregnant  
- 
Incarcerated  
  
DESIGN:   
All patients will be enrolled in the observational arm of the study.  This portion will examine anti-Xa 
levels in response to fixed dose unfractionated heparin drips at 500 units per hour.  
  
Patients with out of range (0.1-0.35 IU/mL) anti-Xa levels will cross over to the interventional arm of the 
study.  These patients will receive real time unfractionated heparin dose adjustment and repeat lab 
draws.  
  
STUDY PROCEDURES:   
During the vascular or microvascular procedure, the attending surgeon will determine whether or not 
the patient will require a fixed dose heparin drip postoperatively. We will enroll a convenience sample 
of patients placed on fixed dose heparin drip by their surgeons—we will not dictate any portions of the 
patient’s care intraoperatively, but rather will study patients already placed on a study-specific regimen 
by their attending surgeon.  Once the order has been placed, the patient will be approached about 
joining the study and sign a consent form if agreeing to participate. Patients will be identified through an 


alert in TheraDoc. If enrolled, the heparin drip will be managed according to the pilot protocol 
developed to maintain a target anti-Xa of 0.1-0.35 IU/mL until discontinued by the attending physician.    
  
Standard of Care vs. Research-Related Procedures:   
Current practice at the University of Utah Hospital for selected microsurgical procedures is to initiate a 
heparin drip for patients determined to be high risk for microvascular thrombosis at a fixed rate of 500 
units/hour, regardless of patient weight, with no monitoring by PTT or anti-xa.   
  
Patients will be monitored using anti-xa levels and heparin infusion rates will be adjusted to maintain a 
target anti-xa of 0.1-0.35 units/mL.   
  
STATISTICAL METHODS, DATA ANALYSIS AND INTERPRETATION:   
- 
Sample estimate  
o An estimate of five patients per month is anticipated for the pilot study period (October 
1, 2016 to March 1, 2017) for a total of 25 patients.  
  
- 
Data analysis  
o Continuous data will be analyzed using the student’s t-test.  
o Categorical data will be analyzed by the Fisher’s exact test.  
  
- 
Power calculation  
o This is a pilot study whose explicit purpose is to generate preliminary data on 
pharmacodynamics of intravenous heparin drips at 500 units/hour, as well as the impact 
of a pharmacist-drive dose adjustment algorithm. By definition, pilot studies do not 
require power calculations as they are exploratory in nature.