Safety and Dose Finding Study of Xigris in Hemodialysis Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the safety of Xigris (Drotrecogin alfa) as an anticoagulant at different dose levels during dialysis treatment in patients with End Stage Renal Disease (ESRD).

Detailed Description
-----------------
In United States, there are over 300,000 patients with ESRD who require hemodialysis. Clinical hemodialysis takes place three times a week and is dependent on adequate anticoagulation throughout the three to four hour procedure. Infection is one of the most common causes of death for patients with ESRD treated with hemodialysis (25%). Xigris (drotrecogin alfa activated) is a recombinant form of human activated protein C and is successfully used for treatment of adult patients with severe sepsis. In addition to its fibrinolytic properties, drotrecogin alpha has both an anti-inflammatory effect, and an anti-coagulant effect. However, there are few safety and no efficacy data on the effect of Xigris in ESRD patients as an anticoagulant.

Official Title
-----------------
Safety and Dose Finding Study of Xigris (Drotrecogin Alfa Activated) as an Anti-coagulant in End Stage Renal Disease (ESRD) Patients Treated With Hemodialysis (HD)

Conditions
-----------------
End Stage Renal Disease

Intervention / Treatment
-----------------
* Drug: Drotrecogin alfa activated (Xigris)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: >18 Usually used heparin with HD Exclusion Criteria: Plt <100 Pregnancy H/o bleeding diathesis H/o CVA Pt on Ticlid/plavix/warfarin SBP >200 BASELINE PTT>50 INR>1.6

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xigris<br>Drotrecogin alfa activated (Xigris) used as anticoagulant in patients treated with hemodialysis. | Drug: Drotrecogin alfa activated (Xigris)<br>* We will test different dose regimens of Drotrecogin alfa activated (Xigris) to determine the optimal dose to achieve PTT between 65 and 100 secs. The initial patients will receive Xigris dosed at an infusion rate of 12 mcg/kg/h via pre-filter arterial drip chamber via a standard IV pump. The PTT will be assessed at baseline,15,30,60,120 and 180 mins. Xigris dose will be adjusted in the following patients if the afferent PTT rises above 100 secs (normal range 25-40 secs) or if PTT remains <65 secs. If PTT remains less than 65 secs, the dose will be increased to the second dose regiment of 18 mcg/kg/hr. The dose escalation will continue in increments of 6 mcg/kg/h to a maximum dose of 36 mcg/kg/h. Each patient will receive Xigris only once.<br>* Other names: Drotrecogin alfa (activated);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Partial Thromboplastin Time (PTT) at 15 Minutes | PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. | PTT level at 15 minutes after start up of Xigris during the hemodialysis treatment. | 
| Mean Partial Thromboplastin Time (PTT) at 30 Minutes | PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. | PTT level at 30 minutes after start up of Xigris during the hemodialysis treatment. | 
| Mean Partial Thromboplastin Time (PTT) at 60 Minutes | PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. | PTT level at 60 minutes after start up of Xigris during the hemodialysis treatment. | 
| Mean Partial Thromboplastin Time (PTT) at 120 Minutes | PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. | PTT level at 120 minutes after start up of Xigris during the hemodialysis treatment. | 
| Mean Partial Thromboplastin Time (PTT) at 180 Minutes | PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. | PTT level at 180 minutes after start up of Xigris during the hemodialysis treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Xigris, Hemodialysis, Anticoagulation, PTT