Safety and Dose Finding Study of Xigris in Hemodialysis Patients

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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01227187

Acronym

Xigris1003

Enrollment

Registered

2010-10-25

Start date

2008-10-31

Completion date

2010-12-31

Last updated

2022-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

End Stage Renal Disease

Keywords

Hemodialysis, Anticoagulation, Xigris, PTT

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).

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.

Interventions

DRUGDrotrecogin 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Mean Partial Thromboplastin Time (PTT) at 15 Minutes	PTT level at 15 minutes after start up of Xigris during the hemodialysis treatment.	PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant.
Mean Partial Thromboplastin Time (PTT) at 30 Minutes	PTT level at 30 minutes after start up of Xigris during the hemodialysis treatment.	PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant.
Mean Partial Thromboplastin Time (PTT) at 60 Minutes	PTT level at 60 minutes after start up of Xigris during the hemodialysis treatment.	PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant.
Mean Partial Thromboplastin Time (PTT) at 120 Minutes	PTT level at 120 minutes after start up of Xigris during the hemodialysis treatment.	PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant.
Mean Partial Thromboplastin Time (PTT) at 180 Minutes	PTT level at 180 minutes after start up of Xigris during the hemodialysis treatment.	PTT level during a hemodialysis treatment will be used to assess the effectiveness of Xigris as an anticoagulant.

Countries

United States

Participant flow

Recruitment details

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

Pre-assignment details

Participants were evaluated for inclusion and exclusion criteria and immediately enrolled in the study.

Participants by arm

Arm	Count
Infusion Rate of 12 mcg/kg/h	1
Infusion Rate of 18 mcg/kg/h	3
Infusion Rate of 24 mcg/kg/h	3
Infusion Rate of 30 mcg/kg/h	5
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Physician Decision	0	0	0	1

Baseline characteristics

Characteristic	Infusion Rate of 12 mcg/kg/h	Infusion Rate of 18 mcg/kg/h	Infusion Rate of 24 mcg/kg/h	Infusion Rate of 30 mcg/kg/h	Total
Age, Continuous	38 years STANDARD_DEVIATION 0	46 years STANDARD_DEVIATION 21.3	48.7 years STANDARD_DEVIATION 13.1	53.2 years STANDARD_DEVIATION 7.9	49 years STANDARD_DEVIATION 12.6
BUN	26 mg/dL STANDARD_DEVIATION 0	36.3 mg/dL STANDARD_DEVIATION 9.5	47 mg/dL STANDARD_DEVIATION 17.4	53.2 mg/dL STANDARD_DEVIATION 17.1	45.2 mg/dL STANDARD_DEVIATION 17.1
Congestive heart failure	0 Participants	0 Participants	1 Participants	2 Participants	3 Participants
Creatinine	15 μmol/L STANDARD_DEVIATION 0	7.8 μmol/L STANDARD_DEVIATION 1.1	7.8 μmol/L STANDARD_DEVIATION 0.5	9.2 μmol/L STANDARD_DEVIATION 3.6	9.0 μmol/L STANDARD_DEVIATION 3
Diabetes	0 Participants	0 Participants	3 Participants	3 Participants	6 Participants
Height	66 inches STANDARD_DEVIATION 0	68.7 inches STANDARD_DEVIATION 2.9	73.3 inches STANDARD_DEVIATION 5.1	68.8 inches STANDARD_DEVIATION 4.1	69.7 inches STANDARD_DEVIATION 4.2
Hematocrit	31.2 Percentage of red blood cells in blood STANDARD_DEVIATION 0	23.2 Percentage of red blood cells in blood STANDARD_DEVIATION 2.5	30.9 Percentage of red blood cells in blood STANDARD_DEVIATION 4	27.9 Percentage of red blood cells in blood STANDARD_DEVIATION 3.6	27.8 Percentage of red blood cells in blood STANDARD_DEVIATION 3.6
Hemoglobin	9.9 g/dL STANDARD_DEVIATION 0	7.2 g/dL STANDARD_DEVIATION 0.6	9.9 g/dL STANDARD_DEVIATION 1.4	9.0 g/dL STANDARD_DEVIATION 1.4	9.0 g/dL STANDARD_DEVIATION 1
International Normalized Ratio	1.1 Ratio STANDARD_DEVIATION 0	1.2 Ratio STANDARD_DEVIATION 0.1	1.2 Ratio STANDARD_DEVIATION 0.2	1.0 Ratio STANDARD_DEVIATION 0.1	1.1 Ratio STANDARD_DEVIATION 0.1
Partial thromboplastin time	38.1 Seconds STANDARD_DEVIATION 0	37.3 Seconds STANDARD_DEVIATION 4.3	37.6 Seconds STANDARD_DEVIATION 1.3	35.5 Seconds STANDARD_DEVIATION 6.1	36.7 Seconds STANDARD_DEVIATION 4.3
Platelets	333 10^9 per liter STANDARD_DEVIATION 0	196.7 10^9 per liter STANDARD_DEVIATION 113.7	315 10^9 per liter STANDARD_DEVIATION 82.3	220.2 10^9 per liter STANDARD_DEVIATION 84.5	247.4 10^9 per liter STANDARD_DEVIATION 95.5
Prothrombin time	13.2 seconds STANDARD_DEVIATION 0	14.6 seconds STANDARD_DEVIATION 0.2	14.2 seconds STANDARD_DEVIATION 1	13.1 seconds STANDARD_DEVIATION 1	13.8 seconds STANDARD_DEVIATION 1
Race/Ethnicity, Customized Black	1 Participants	2 Participants	3 Participants	4 Participants	10 Participants
Race/Ethnicity, Customized White	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Red blood cells	3.6 million/mm^3 STANDARD_DEVIATION 0	2.7 million/mm^3 STANDARD_DEVIATION 0.4	3.4 million/mm^3 STANDARD_DEVIATION 0.9	3.2 million/mm^3 STANDARD_DEVIATION 0.5	3.1 million/mm^3 STANDARD_DEVIATION 0.6
Sex: Female, Male Female	1 Participants	1 Participants	1 Participants	1 Participants	4 Participants
Sex: Female, Male Male	0 Participants	2 Participants	2 Participants	4 Participants	8 Participants
WBC	6.0 10^3/µL STANDARD_DEVIATION 0	5.9 10^3/µL STANDARD_DEVIATION 1.8	8.1 10^3/µL STANDARD_DEVIATION 0.7	6.4 10^3/µL STANDARD_DEVIATION 1.2	6.7 10^3/µL STANDARD_DEVIATION 1.4
Weight	96 kilograms STANDARD_DEVIATION 0	69.6 kilograms STANDARD_DEVIATION 17.6	104.5 kilograms STANDARD_DEVIATION 12.6	79.4 kilograms STANDARD_DEVIATION 29.8	84.6 kilograms STANDARD_DEVIATION 29.7

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 3	0 / 3	0 / 5
other Total, other adverse events	0 / 1	0 / 3	0 / 3	1 / 5
serious Total, serious adverse events	0 / 1	0 / 3	0 / 3	0 / 5