Safety and Dose Finding Study of Xigris in Hemodialysis Patients

End Stage Renal Disease Clinical Trial

— Xigris1003  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227187
• Other study ID #: F1K-MC-1003
• Status: Completed
• Phase: Phase 2
• Start date: October 2008
• Est. completion date: December 2010

Study information

• Verified date: November 2020
• Source: George Washington University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. >18

2. Usually used heparin with HD

Exclusion Criteria:

1. Plt <100

2. Pregnancy

3. H/o bleeding diathesis

4. H/o CVA

5. Pt on Ticlid/plavix/warfarin

6. SBP >200

7. BASELINE PTT>50

8. INR>1.6

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Drotrecogin alfa activated (Xigris)
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.

Locations

Country	Name	City	State
United States	The George Washington University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
George Washington University	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (21)

Bernard GR, Ely EW, Wright TJ, Fraiz J, Stasek JE Jr, Russell JA, Mayers I, Rosenfeld BA, Morris PE, Yan SB, Helterbrand JD. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med. 2001 Nov;29(11):2051-9. — View Citation

Bernard GR, Macias WL, Joyce DE, Williams MD, Bailey J, Vincent JL. Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis. Crit Care. 2003 Apr;7(2):155-63. Epub 2003 Feb 28. Review. — View Citation

Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. — View Citation

Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999 Apr;55(4):1553-9. — View Citation

Bologa RM, Levine DM, Parker TS, Cheigh JS, Serur D, Stenzel KH, Rubin AL. Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis. 1998 Jul;32(1):107-14. — View Citation

Causes of death. USRDS. United States Renal Data System. Am J Kidney Dis. 1997 Aug;30(2 Suppl 1):S107-17. — View Citation

Hakim RM, Breyer J, Ismail N, Schulman G. Effects of dose of dialysis on morbidity and mortality. Am J Kidney Dis. 1994 May;23(5):661-9. — View Citation

Hakim RM, Held PJ, Stannard DC, Wolfe RA, Port FK, Daugirdas JT, Agodoa L. Effect of the dialysis membrane on mortality of chronic hemodialysis patients. Kidney Int. 1996 Aug;50(2):566-70. — View Citation

Held PJ, Port FK, Webb RL, Wolfe RA, Bloembergen WE, Turenne MN, Holzman E, Ojo AO, Young EW, Mauger EA, et al. Excerpts from United States Renal Data System 1995 Annual Data Report. Am J Kidney Dis. 1995 Oct;26(4 Suppl 2):S1-186. — View Citation

Held PJ, Port FK, Wolfe RA, Stannard DC, Carroll CE, Daugirdas JT, Bloembergen WE, Greer JW, Hakim RM. The dose of hemodialysis and patient mortality. Kidney Int. 1996 Aug;50(2):550-6. — View Citation

Kaysen GA. Biological basis of hypoalbuminemia in ESRD. J Am Soc Nephrol. 1998 Dec;9(12):2368-76. Review. — View Citation

Kaysen GA. C-reactive protein: a story half told. Semin Dial. 2000 May-Jun;13(3):143-6. — View Citation

Kaysen GA. Role of inflammation and its treatment in ESRD patients. Blood Purif. 2002;20(1):70-80. Review. — View Citation

Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz I, Veis JH. Psychosocial factors, behavioral compliance and survival in urban hemodialysis patients. Kidney Int. 1998 Jul;54(1):245-54. — View Citation

Kimmel PL, Phillips TM, Simmens SJ, Peterson RA, Weihs KL, Alleyne S, Cruz I, Yanovski JA, Veis JH. Immunologic function and survival in hemodialysis patients. Kidney Int. 1998 Jul;54(1):236-44. — View Citation

Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med. 1981 Nov 12;305(20):1176-81. — View Citation

Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990 May;15(5):458-82. — View Citation

Owen WF Jr, Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med. 1993 Sep 30;329(14):1001-6. — View Citation

Owen WF, Lowrie EG. C-reactive protein as an outcome predictor for maintenance hemodialysis patients. Kidney Int. 1998 Aug;54(2):627-36. — View Citation

Patient mortality and survival. USRDS. United State Renal Data System. Am J Kidney Dis. 1997 Aug;30(2 Suppl 1):S86-106. — View Citation

Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis. 2000 Mar;35(3):469-76. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.