Effect of An Oral Absorbent AST-120 in Late-stage Chronic Kidney Disease (CKD) Patients.

Recent research work has directed especial attention toward a distinct group of uremic retension molecules, called "protein-bound uremic toxins". The prototypes of this group of uremic toxins are indoxyl sulfate and p-cresol. These uremic toxins can promote production of free radical and impair antioxidant system and exerts direct toxicity on different cells and organs, including mesangial, tubular, endothelial cell and osteoblasts. Accumulation of these protein bound uremic toxins results in glomerular sclerosis and interstitial fibrosis of kidneys of uremic rats and confer skeletal resistance to parthyroid hormone in uremic patients. In hemodialysis, high serum p-cresol level is associated with higher cardiovascular mortality.

AST-120 (Kremezin) is a carbonated oral absorbent extensively used in Japan and Korea. It has superior adsorption ability for certain small-molecular weight organic compounds known to accumulate in patients with CKD. In uremic rats and CKD patients, oral administration of AST-120 decreased the elevated pretreatment levels of serum indoxyl sulfate. In Japan, it was reported that AST-120 suppressed the increase in serum creatinine levels, prevented proteinuria, improved uremic symptoms, and, consequently, led to the postponement of dialysis therapy.

Value of AST-120 on the outcome of late-stage CKD patients is still unknown. We hypothesized AST-120 through reduction of level of indoxyl sulfate and p-cresol can improved the morbidity- mortality of CKD patients.

The principal aim of this prospective cohort study is to investigate the effectiveness of AST-120 in incidence of dialysis and mortality of late-stage CKD patients. Determination of this relationship can help to establish new therapeutic strategy in the treatment of late-stage CKD patients.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; AST-120
• Intervention / Treatment: Drug: AST-120

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Keelung, Taiwan, 204
    • Department of Nephrology, Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adults aged > 18 year-old or < 85 year-old
• eGFR or CCR < 60 ml/min
• hemoglobin < 10 g/dL, ESA-naïve, had adequate iron storage (serum ferritin > 200 ng/dL and transferrin saturation > 20%)
• no spontaneous renal improvement or progression in past 3 months.

Exclusion Criteria:

• renal transplant recipients, liver cirrhosis, bone marrow disorder
• blood pressure > 170/80 mmHg in 3 occasions
• recent cardiovascular disease (Coronary artery disease, myocardial ischemia, cerebrovascular disease or peripheral artery disease) or gastrointestinal bleeding in past 3 months
• acute tubular necrosis in the past 3 months
• unwilling to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 2
Experimental: AST-120 group; Administration of AST-120	Drug: AST-120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
renal function change	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
anemia	1 year

Other Outcome Measures

Outcome Measure	Time Frame
lipid profile and uric acid	1 year

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: I-Wen Wu, MD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 5, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Estimate): August 6, 2013
• Last Update Submitted That Met QC Criteria: August 3, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: IWW-0004; 98-794A3 (Other Grant/Funding Number: Conmed)