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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Xigris | Experimental | Drotrecogin alfa activated (Xigris) used as anticoagulant in patients treated with hemodialysis. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lakhmir S Chawla, MD | George Washington University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The George Washington University Hospital | Washington D.C. | District of Columbia | 20037 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8840287 | Background | 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. | |
| 8172208 | 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. |
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Participants were evaluated for inclusion and exclusion criteria and immediately enrolled in the study.
The study was conducted on stable inpatient HD patients between October 2008 and September 2010. The study design was based on different possible dose levels of APC infusion: 12, 18, 24, 30 μg/kg/h. The initial starting dose of APC for the first patient was 12 μg/kg/h. When a study patient's PTT was <60 s, the starting dose for the next study patient was increased by 6. There were no patient's in the 30 μg/kg/h group with a PTT of <60 s
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| ID | Title | Description |
|---|---|---|
| FG000 | APC Initiation Dose of 12 μg/kg/h | Activated protein C initiation dose of 12 μg/kg/h for the first patient |
| FG001 | APC Initiation Dose of 18 μg/kg/h | Activated protein C initiation dose of 18 μg/kg/h |
| FG002 | APC Initiation Dose of 24 μg/kg/h | Activated protein C initiation dose of 24 μg/kg/h |
| FG003 | APC Initiation Dose of 30 μg/kg/h | Activated protein C initiation dose of 30 μg/kg/h |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Infusion Rate of 12 mcg/kg/h | |
| BG001 | Infusion Rate of 18 mcg/kg/h | |
| BG002 | Infusion Rate of 24 mcg/kg/h |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | Seconds | PTT level at 15 minutes after start up of Xigris during the hemodialysis treatment. |
|
Enrollment until post-treatment day 14
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APC Initiation Dose 12 μg/kg/h | APC initiation dose 12 μg/kg/h | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe intradialytic hypertension | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lakhmir Chawla | George Washington University | 202-715-4752 | lchawla@mfa.gwu.edu |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C421124 | drotrecogin alfa activated |
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|
| 7573030 | 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. |
| 8840285 | 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. |
| 9648085 | 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. |
| 7027040 | 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. |
| 2333868 | 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. |
| 8366899 | 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. |
| 9259696 | 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. |
| 9648084 | 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. |
| 10692273 | 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. |
| 9848794 | Background | Kaysen GA. Biological basis of hypoalbuminemia in ESRD. J Am Soc Nephrol. 1998 Dec;9(12):2368-76. doi: 10.1681/ASN.V9122368. |
| 9259695 | 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. |
| 11803162 | Background | Kaysen GA. Role of inflammation and its treatment in ESRD patients. Blood Purif. 2002;20(1):70-80. doi: 10.1159/000046988. |
| 9669431 | 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. |
| 10833771 | 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. |
| 9690231 | 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. |
| 10201022 | 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. |
| 11236773 | 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. |
| 11700394 | 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. |
| 12720562 | 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. |
| BG003 | Infusion Rate of 30 mcg/kg/h |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | inches |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Diabetes | Count of Participants | Participants |
|
| Congestive heart failure | Count of Participants | Participants |
|
| WBC | Mean | Standard Deviation | 10^3/µL |
|
| Red blood cells | Mean | Standard Deviation | million/mm^3 |
|
| Hemoglobin | Mean | Standard Deviation | g/dL |
|
| Hematocrit | Mean | Standard Deviation | Percentage of red blood cells in blood |
|
| Platelets | Mean | Standard Deviation | 10^9 per liter |
|
| BUN | Mean | Standard Deviation | mg/dL |
|
| Creatinine | Mean | Standard Deviation | μmol/L |
|
| Prothrombin time | Mean | Standard Deviation | seconds |
|
| Partial thromboplastin time | Mean | Standard Deviation | Seconds |
|
| International Normalized Ratio | Mean | Standard Deviation | Ratio |
|
APC Initiation dose 24 μg/kg/h
| OG003 | APC Initiation Dose 30 μg/kg/h | APC Initiation dose 30 μg/kg/h |
|
|
| 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. | Posted | Mean | Standard Deviation | Seconds | 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. | Posted | Mean | Standard Deviation | Seconds | 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. | Posted | Mean | Standard Deviation | Seconds | 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. | Posted | Mean | Standard Deviation | Seconds | PTT level at 180 minutes after start up of Xigris during the hemodialysis treatment. |
|
|
|
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | APC Initiation Dose 18 μg/kg/h | APC initiation dose 18 μg/kg/h | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | APC Initiation Dose 24 μg/kg/h | APC initiation dose 24 μg/kg/h | 0 | 3 | 0 | 3 | 0 | 3 |
| EG003 | APC Initiation Dose 30 μg/kg/h | APC initiation dose 30 μg/kg/h | 0 | 5 | 0 | 5 | 1 | 5 |
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |