Safety and Dose Finding Study of Xigris in Hemodialysis Patients

NCT01227187 | Completed Phase 2 Results

• 1 other identifier: F1K-MC-1003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

End Stage Renal Disease

Keywords

Hemodialysis; Anticoagulation; Xigris; PTT

Outcome Measures

Primary Outcomes (5)

• 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.

Study Arms (1)

Xigris

EXPERIMENTAL

Drotrecogin alfa activated (Xigris) used as anticoagulant in patients treated with hemodialysis.

Drug: Drotrecogin alfa activated (Xigris)

Interventions

Drotrecogin alfa activated (Xigris) DRUG

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.

Also known as: Drotrecogin alfa (activated)

Xigris

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18
• Usually used heparin with HD

You may not qualify if:

• Plt \<100
• Pregnancy
• H/o bleeding diathesis
• H/o CVA
• Pt on Ticlid/plavix/warfarin
• SBP \>200
• BASELINE PTT\>50
• INR\>1.6

Sponsors & Collaborators

• George Washington University: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

The George Washington University Hospital

Washington D.C., District of Columbia, 20037, United States

Location

Related Publications (21)

• 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. doi: 10.1038/ki.1996.350.

  PMID: 8840287 BACKGROUND

• 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. doi: 10.1016/s0272-6386(12)70276-7.

  PMID: 8172208 BACKGROUND

• 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.

  PMID: 7573030 BACKGROUND

• 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. doi: 10.1038/ki.1996.348.

  PMID: 8840285 BACKGROUND

• 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. doi: 10.1046/j.1523-1755.1998.00989.x.

  PMID: 9648085 BACKGROUND

• Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription on patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med. 1981 Nov 12;305(20):1176-81. doi: 10.1056/NEJM198111123052003.

  PMID: 7027040 BACKGROUND

• 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. doi: 10.1016/s0272-6386(12)70364-5.

  PMID: 2333868 BACKGROUND

• 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. doi: 10.1056/NEJM199309303291404.

  PMID: 8366899 BACKGROUND

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

  PMID: 9259696 BACKGROUND

• 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. doi: 10.1046/j.1523-1755.1998.00981.x.

  PMID: 9648084 BACKGROUND

• 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. doi: 10.1016/s0272-6386(00)70200-9.

  PMID: 10692273 BACKGROUND

• Kaysen GA. Biological basis of hypoalbuminemia in ESRD. J Am Soc Nephrol. 1998 Dec;9(12):2368-76. doi: 10.1681/ASN.V9122368.

  PMID: 9848794 BACKGROUND

• 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.

  PMID: 9259695 BACKGROUND

• Kaysen GA. Role of inflammation and its treatment in ESRD patients. Blood Purif. 2002;20(1):70-80. doi: 10.1159/000046988.

  PMID: 11803162 BACKGROUND

• 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. doi: 10.1053/ajkd.1998.v32.pm9669431.

  PMID: 9669431 BACKGROUND

• Kaysen GA. C-reactive protein: a story half told. Semin Dial. 2000 May-Jun;13(3):143-6. doi: 10.1046/j.1525-139x.2000.00038.x. No abstract available.

  PMID: 10833771 BACKGROUND

• Owen WF, Lowrie EG. C-reactive protein as an outcome predictor for maintenance hemodialysis patients. Kidney Int. 1998 Aug;54(2):627-36. doi: 10.1046/j.1523-1755.1998.00032.x.

  PMID: 9690231 BACKGROUND

• Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999 Apr;55(4):1553-9. doi: 10.1046/j.1523-1755.1999.00391.x.

  PMID: 10201022 BACKGROUND

• 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. doi: 10.1056/NEJM200103083441001.

  PMID: 11236773 BACKGROUND

• 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. doi: 10.1097/00003246-200111000-00003.

  PMID: 11700394 BACKGROUND

• 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. doi: 10.1186/cc2167. Epub 2003 Feb 28.

  PMID: 12720562 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

drotrecogin alfa activated

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Lakhmir Chawla
• Organization: George Washington University

lchawla@mfa.gwu.edu

202-715-4752

Study Officials

• Lakhmir S Chawla, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: October 25, 2010
• Study Start: October 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 3, 2022
• Results First Posted: February 3, 2022

Record last verified: 2020-11

Locations

US (1)