Safety and Dose Finding Study of Xigris in Hemodialysis Patients - Full Text View

Purpose

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).

Condition	Intervention	Phase
End Stage Renal Disease	Drug: Drotrecogin alfa activated	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners Dialysis Kidney Failure

Drug Information available for: Drotrecogin alfa

U.S. FDA Resources

Further study details as provided by George Washington University:

Primary Outcome Measures:

Change in the level of Partial Thromboplastin Time (PTT). [ Time Frame: PTT level at 15 minutes after start up of Xigris during the hemodialysis treatment. ] [ Designated as safety issue: Yes ]
PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. The goal of the study is to maintain the PTT level between 65-100 seconds during the treatment. If PTT is <60 or >100, the dose will be adjusted by 6 mcg/kg/h in the consecutive patient to a minimum dose of 12 mcg/kg/h or up to a maximum dose of 36 mcg/kg/h.
Change in the level of Partial Thromboplastin Time (PTT). [ Time Frame: PTT level at 30 minutes after start up of Xigris during the hemodialysis treatment ] [ Designated as safety issue: Yes ]
PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. The goal of the study is to maintain the PTT level between 65-100 seconds during the treatment. If PTT is <60 or >100, the dose will be adjusted by 6 mcg/kg/h in the consecutive patient to a minimum dose of 12 mcg/kg/h or up to a maximum dose of 36 mcg/kg/h.
Change in the level of Partial Thromboplastin Time (PTT). [ Time Frame: PTT level at 60 minutes after start up of Xigris during the hemodialysis treatment. ] [ Designated as safety issue: Yes ]
PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. The goal of the study is to maintain the PTT level between 65-100 seconds during the treatment. If PTT is <60 or >100, the dose will be adjusted by 6 mcg/kg/h in the consecutive patient to a minimum dose of 12 mcg/kg/h or up to a maximum dose of 36 mcg/kg/h.
Change in the level of Partial Thromboplastin Time (PTT). [ Time Frame: PTT level at 120 minutes after start up of Xigris during the hemodialysis treatment. ] [ Designated as safety issue: Yes ]
PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. The goal of the study is to maintain the PTT level between 65-100 seconds during the treatment. If PTT is <60 or >100, the dose will be adjusted by 6 mcg/kg/h in the consecutive patient to a minimum dose of 12 mcg/kg/h or up to a maximum dose of 36 mcg/kg/h.
Change in the level of Partial Thromboplastin Time (PTT). [ Time Frame: PTT level at 180 minutes after start up of Xigris during the hemodialysis treatment. ] [ Designated as safety issue: Yes ]
PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant. The goal of the study is to maintain the PTT level between 65-100 seconds during the treatment. If PTT is <60 or >100, the dose will be adjusted by 6 mcg/kg/h in the consecutive patient to a minimum dose of 12 mcg/kg/h or up to a maximum dose of 36 mcg/kg/h.

Enrollment:	12
Study Start Date:	October 2008
Study Completion Date:	December 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Xigris Xigris used as anticoagulant in patients treated with hemodialysis.	Drug: Drotrecogin alfa activated We plan to determine the optimal dose of Xigris needed to achieve PTT between 65 and 100 secs. The study will test different dose regimens of Xigris. The initial patients will receive Xigris dosed at an infusion rate of 12 mcg/kg/h via the pre-filter arterial drip chamber via a standard intravenous pump. The PTT will be assessed from blood samples drawn at baseline,15,30,60,120 and 180 mins. The dose of Xigris 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. Other Name: Drotrecogin alfa (activated)

Arms

Assigned Interventions

Experimental: Xigris

Xigris used as anticoagulant in patients treated with hemodialysis.

Drug: Drotrecogin alfa activated

We plan to determine the optimal dose of Xigris needed to achieve PTT between 65 and 100 secs. The study will test different dose regimens of Xigris. The initial patients will receive Xigris dosed at an infusion rate of 12 mcg/kg/h via the pre-filter arterial drip chamber via a standard intravenous pump. The PTT will be assessed from blood samples drawn at baseline,15,30,60,120 and 180 mins. The dose of Xigris 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.

Other Name: Drotrecogin alfa (activated)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227187

Locations

United States, District of Columbia
The George Washington University Hospital
Washington, District of Columbia, United States, 20037

Sponsors and Collaborators

George Washington University

Eli Lilly and Company

Investigators

Principal Investigator:

Lakhmir S Chawla, MD

George Washington University

More Information

Publications:

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.

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.

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. No abstract available.

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.

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.

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.

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.

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.

[No authors listed] Causes of death. USRDS. United States Renal Data System. Am J Kidney Dis. 1997 Aug;30(2 Suppl 1):S107-17. No abstract available.

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.

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.

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

[No authors listed] Patient mortality and survival. USRDS. United State Renal Data System. Am J Kidney Dis. 1997 Aug;30(2 Suppl 1):S86-106. No abstract available.

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

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.

Kaysen GA. C-reactive protein: a story half told. Semin Dial. 2000 May-Jun;13(3):143-6. No abstract available.

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

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

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.

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.

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.

Responsible Party:	Lakhmir Chawla, Associate Professor, George Washington University
ClinicalTrials.gov Identifier:	NCT01227187 History of Changes
Other Study ID Numbers:	F1K-MC-1003
Study First Received:	July 14, 2010
Last Updated:	July 20, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by George Washington University:

Hemodialysis
Anticoagulation
Xigris
PTT

Additional relevant MeSH terms:

Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Anticoagulants
Protein C
Drotrecogin alfa activated

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 21, 2013

Safety and Dose Finding Study of Xigris in Hemodialysis Patients (Xigris1003)