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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Lakhmir Chawla, George Washington University
ClinicalTrials.gov Identifier:
NCT01227187
First received: July 14, 2010
Last updated: July 20, 2012
Last verified: July 2012
  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:


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)

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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

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 August 21, 2014