Safety and Efficacy Study of the Effect of Etanercept in Hemodialysis Patients

• Sponsor: Kaysen, George A., M.D., Ph.D. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00293202
• Collaborator: Amgen (Industry), Dialysis Clinic, Inc. (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 65
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Etanercept is a novel anti-inflammatory agent currently used in patients with rheumatoid arthritis. We are examining whether Etanercept is effective in improving the nutritional status of hemodialysis patients as a consequence of its ability to decrease inflammation.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Drug: Etanercept; Drug: Placebo	Phase 2

Detailed Description

Hemodialysis patients with end stage renal disease have a high mortality rate. In individual patients, mortality is associated with a low serum albumin concentration, a marker of poor nutritional status, and with elevated C-reactive protein, a marker of inflammation. Since efforts to improve nutrition through dietary intake have not been successful, inflammation is thought to play a key role in determining nutritional status. Recently, it has been shown that malnutrition, inflammation, and atherosclerosis are closely related in patients with chronic renal failure. It is our hypothesis that suppression of the cycle of inflammation, malnutrition, and vascular injury caused by atherosclerosis will improve survival in dialysis patients. This study is designed to examine whether suppression of the inflammatory response can be accomplished safely with Etanercept and to determine if this suppression will improve nutritional status and clinical outcome in hemodialysis patients with poor nutritional status and evidence of inflammation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a double blind study- one group received 25mg Etanercept twice per week; the other is control - receiving saline twice per weekThis is a double blind study- one group received 25mg Etanercept twice per week; the other is control - receiving saline twice per week
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double Blind Study
• Primary Purpose: Treatment
• Official Title: The Effect of Etanercept in Suppression of the Systemic Inflammatory Response in Hemodialysis Patients
• Actual Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Etanercept 25 mg Etanercept 25 mg injection twice a week	Drug: Etanercept; Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week; Other Names: Enbrel
Placebo Comparator: Saline Saline injection twice a week	Drug: Placebo; Hemodialysis patients will receive Saline by subcutaneous injection twice a week; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Albumin [52 weeks]

   An increased serum albumin (ALB) concentration expected. Higher concentrations of Albumin indicate better outcome. Normal ranges of Albumin in this study is from 3.5 to 5.5 gram per deciliter (g/dL). We expect ALB to remain or increase in this study.

2. C-reactive Protein [52 weeks]

   A reduced C-reactive protein (CRP) concentration is expected.

Secondary Outcome Measures

1. Prealbumin (mg/dL) [52 weeks]

   Effect of treatment on prealbumin (PAB) concentration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Presence of end stage renal disease

Exclusion Criteria:

• History of Tuberculosis History of Recurrent Infection Recent AMI, Cancer within previous 5 years Presence of Hepatitis B, Hepatitis C, HIV, systemic lupus erythematosis, presence of transcutaneous access (external catheter)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Davis, Medical Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• Kaysen, George A., M.D., Ph.D.
• Amgen
• Dialysis Clinic, Inc.

Investigators

• Principal Investigator: George Kaysen, MD, PhD, University of California, Davis

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 9, 2021

More Information

Additional Information:

• B.R. Don, K.Kim, J. Li, T. Dwyer, F. Alexander and G.A. Kaysen.The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients. 2010; 73: 431-438. doi: 10.5414/CNP73431

Publications

None provided.

• Responsible Party: George A. Kaysen, M.D., Ph.D., Professor, Kaysen, George A., M.D., Ph.D.
• ClinicalTrials.gov Identifier: NCT00293202
• Other Study ID Numbers: 200311904
• First Posted: Feb 17, 2006
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by George A. Kaysen, M.D., Ph.D., Professor, Kaysen, George A., M.D., Ph.D.: etanercept; malnutrition; inflammation; hemodialysis
• Additional relevant MeSH terms: Kidney Failure, Chronic; Etanercept

Study Results

Participant Flow

Recruitment Details	The protocol was approved by the Human Subjects Review Committee of the University of California Davis Medical Center and Dialysis Clinics, Incorporated. Screening started in January 2005, and had to be terminated early due to low enrollment in December 2006
Pre-assignment Detail	Subject was consented and screened for safety. Then they have to qualify for 3 monthly screening values. Once deemed qualified for the study, subject then randomized into a double-blind study; to follow regimen of protocols and followed to 52 weeks of study.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description	Active Comparator: Etanercept 25 mg injection twice a week 5 Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week Do not have active infections Patient will be followed for 52 weeks	Placebo comparator: Saline injection twice a week 5 Hemodialysis patients will receive Saline by subcutaneous injection twice a week Do not have active infections Patient will be followed for 52 weeks
Period Title: Overall Study
STARTED	5	5
COMPLETED	2	3
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Etanercept	Placebo	Total
Arm/Group Description	Etanercept 25 mg injection twice a week Etanercept: Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week	Saline injection twice a week Placebo: Hemodialysis patients will receive Saline by subcutaneous injection twice a week	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 80%	3 60%	7 70%
>=65 years	1 20%	2 40%	3 30%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	51 (16.739)	55 (15.209)	53 (15.101)
Sex: Female, Male (Count of Participants)
Female	1 20%	2 40%	3 30%
Male	4 80%	3 60%	7 70%
Region of Enrollment (Participant) [Number]
United States	5	5	10
C-Reactive Protein (CRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	29.05 (15.60)	10.98 (3.95)	15.79 (28.13)
Albumin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.39 (0.24)	3.31 (0.21)	3.37 (0.20)

Outcome Measures

1. Primary Outcome

Title	Albumin
Description	An increased serum albumin (ALB) concentration expected. Higher concentrations of Albumin indicate better outcome. Normal ranges of Albumin in this study is from 3.5 to 5.5 gram per deciliter (g/dL). We expect ALB to remain or increase in this study.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Hemodialysis patients have a high mortality rate caused by poor nutrition and inflammation. The hypothesis is that suppression of inflammation reverses the malnutrition-inflammation syndrome in hemodialysis patients. Etanercept is an anti-inflammatory agent. Thus it is expected that participant given Etanercept will have a reduced amount of inflammation in their bodies and have better nutritional status - indicated by an increase/steady Albumin level.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description	Active comparator: Etanercept 25 mg injection twice a week Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week for a total of 52 weeks.	No Drug: Saline injection twice a week Hemodialysis patients will receive Saline by subcutaneous injection twice a week for a total of 52 weeks
Measure Participants	5	5
Mean (Standard Deviation) [g/dL]	3.34 (0.22)	3.42 (0.25)

2. Primary Outcome

Title	C-reactive Protein
Description	A reduced C-reactive protein (CRP) concentration is expected.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Malnutrition, inflammation, and atherosclerosis affect patients with chronic renal failure. High C-reactive protein is a marker of inflammation. This study is designed to examine whether suppression of the inflammatory response can be accomplished safely with Etanercept. For those who has high CRP level, we expect that CRP level will be reduced

Arm/Group Title	Etanercept	Placebo
Arm/Group Description	Active comparator: Etanercept 25 mg injection twice a week Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week for a total of 52 weeks	No Drug - Saline injection twice a week Hemodialysis patients will receive Saline by subcutaneous injection twice a week for a total of 52 weeks
Measure Participants	5	5
Mean (Standard Deviation) [mg/L]	28.96 (26.00)	11.94 (13.53)

3. Secondary Outcome

Title	Prealbumin (mg/dL)
Description	Effect of treatment on prealbumin (PAB) concentration
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Serum Prealbumin is measured in milligram per deciliter (mg/dL). Increase number is a measured of better nutritional status. In the etanercept group we would expect fewer decreases in prealbumin. Decreased level of prealbumin may indicate inflammations may be occurring in the body.

Arm/Group Title	Etanercept 25 mg	Saline
Arm/Group Description	Etanercept 25 mg injection twice a week Etanercept: Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week	Saline injection twice a week Placebo: Hemodialysis patients will receive Saline by subcutaneous injection twice a week
Measure Participants	5	5
Mean (Standard Deviation) [mg/dL]	32.36 (8.64)	31.43 (8.83)

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	Adverse Event collected was in the same category as defined
Arm/Group Title	Etanercept		Placebo
Arm/Group Description	Etanercept 25 mg injection twice a week Etanercept: Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week		Saline injection twice a week Placebo: Hemodialysis patients will receive Saline by subcutaneous injection twice a week
All Cause Mortality
	Etanercept		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Etanercept		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		3/5 (60%)
Cardiac disorders
CABG	0/5 (0%)	0	1/5 (20%)	1
Ventricular Fibrillation	0/5 (0%)	0	1/5 (20%)	1
Gastrointestinal disorders
Epigastric pain	0/5 (0%)	0	1/5 (20%)	1
Nervous system disorders
Stroke	0/5 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Etanercept		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/5 (20%)
General disorders
Cold symptoms	0/5 (0%)	0	1/5 (20%)	1
Hematuria, chest pain, nausea and vomiting	1/5 (20%)	1	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Skin pain	0/5 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Only 10 out of 40 subjects recruited. Only 5 out of 10 subject randomized completed the study. The study has been slow to accrue patients due to the large number and stringent inclusion and exclusion criteria so as to optimize safety. This is due to Etanercept as an anti-inflammatory agent that acts directly on a key regulatory protein in the immune system, tumor necrosis factor α. Extreme stringency was intended to prevent the potential unmasking of latent infection.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.