Clinical trial NCT00500682: A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease (EPPIC-1)
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of AST-120 for Prevention of Chronic Kidney Disease Progression in Patients With Moderate to Severe Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: Kidney Diseases
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
Collaborators: name: Kureha Corporation
First posted: 2007-07-13
Enrollment: 1020
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1) To evaluate the effectiveness of AST-120 (spherical carbon adsorbent) added to standard-of-care therapy in moderate to severe Chronic Kidney Disease (CKD), on time to first occurrence of any event of the triple composite outcome of initiation of dialysis, kidney transplant or doubling of serum creatinine (sCr) when compared with placebo; 2) To evaluate the safety and tolerability of long-term AST-120 therapy in patients with CKD; 3) To evaluate the effects of AST-120 versus placebo, on other measures of renal function.


Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* Moderate to severe CKD, not anticipated to require dialysis or renal transplant within the next 6 months
* Patient survival expected to be no less than one year
* Serum creatinine in men \>= 2.0 mg/dL (\>= 177 µmol/L) and \<= 5.0 mg/dL (\<= 442 µmol/L), and in women \>= 1.5 mg/dL (\>= 133 µmol/L) and \<= 5.0 mg/dL (\<= 442 µmol/L) at Screening
* Urinary total protein to urinary total creatinine ratio must be \>= 0.5 on a spot void at Screening
* Blood pressure \<= 160/90 mmHg at both Screening and Baseline. In addition, blood pressure, if measured, must have been stable in hypertensive patients over the 3 months prior to Screening, with no more than 1 blood pressure reading \> 160/90 mmHg
* In patients being treated for hypertension, they should be on a stable anti-hypertensive regimen

Exclusion Criteria:

* Obstructive or reversible cause of kidney disease
* Nephrotic syndrome defined as a ratio of urinary total protein to urinary creatinine of \> 6.0 as measured on a spot void
* Adult polycystic kidney disease
* History of previous kidney transplant
* History of recent (within the past 6 months) accelerated or malignant hypertension
* Uncontrolled arrhythmia or severe cardiac disease within the past 6 months
* History of malabsorption, inflammatory bowel disease, hiatal hernia, active peptic ulcer, or severe GI dysmotility, not attributable to the use of a phosphate binder
* Received any investigational agent or participated in a clinical study within the previous 3 months
* Presence of any significant medical condition that might create an undue risk with study participation, or significantly confound the collection of safety and efficacy data in this study

Primary outcomes:
measure: Composite of Dialysis Initiation, Kidney Transplantation, and Serum Creatinine Doubling. Number of Participants Meeting the Criteria Are Reported.
timeFrame: Beyond Week 48, a 12-week visit cycle continued until the end of the study or until individual patients reached an endpoint
measure: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
timeFrame: Approximately 42 months
Secondary outcomes:
measure: Number of Participants Who Developed a Component of a Quadruple Composite Endpoint (Initiation of Dialysis, Kidney Transplant, Doubling of sCr, or Death)
timeFrame: Approximately 42 months
measure: Vitamin A Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.615 Days), Final Visit (Mean: 947.354 Days)
measure: Vitamin B12 Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.114 Days), Final Visit (Mean: 947.239 Days)
measure: 25-Hydroxyvitamin D Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 427.270 Days), Final Visit (Mean: 946.762 Days)
measure: Vitamin E Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.056 Days), Final Visit (Mean: 946.525 Days)
measure: Vitamin K Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 441.826 Days), Final Visit (Mean: 946.463 Days)
measure: Serum Folate Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 423.024 Days), Final Visit (Mean: 946.074 Days)
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Alhambra
country: United States
state: California
city: Covina
country: United States
state: California
city: Glendale
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Stamford
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Hudson
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Spring Hill
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Kansas City
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Ypsilanti
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Camden
country: United States
state: New Jersey
city: Eatontown
country: United States
state: New Jersey
city: Port Washington
country: United States
state: New York
city: Springfield Gardens
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Rock Hill
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Appleton
country: United States
state: Wisconsin
city: Oshkosh
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: San Luis
country: Argentina
city: San Pedro
country: Argentina
city: Tucuman
country: Argentina
city: Barao Geraldo-Campinas
country: Brazil
city: Belo Horizonte Minas Gerais
country: Brazil
city: Juiz de Fora
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: São Paulo
country: Brazil
city: Taubaté
country: Brazil
city: Winnipeg
country: Canada
state: Manitoba
city: Brampton
country: Canada
state: Ontario
city: Kitzhener
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Scarborough
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Ceske Budejovice
country: Czechia
city: Jihlava
country: Czechia
city: Ostrava - Poruba
country: Czechia
city: Praha
country: Czechia
city: Tabor
country: Czechia
city: Grenoble
country: France
city: Lyon
country: France
city: Nantes
country: France
city: Saint-Lo
country: France
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Como
country: Italy
city: Pavia
country: Italy
city: Aguascalientes
country: Mexico
city: Mexico City
country: Mexico
city: Tijuana
country: Mexico
city: Gdansk
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Caguas
country: Puerto Rico
city: Bamaul
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Kazan
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Sochi
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Chernovtsy
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zhytomir
country: Ukraine
Study officials:
affiliation: Information at Mitsubishi Tanabe Pharma Development America, Inc.
name: Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Arita K, Kato A, Shimizu M. Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD. J Am Soc Nephrol. 2015 Jul;26(7):1732-46. doi: 10.1681/ASN.2014010042. Epub 2014 Oct 27.
citation: Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Shimizu M, Kikuchi M, Shobu Y. Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120. Clin Exp Nephrol. 2018 Apr;22(2):299-308. doi: 10.1007/s10157-017-1447-0. Epub 2017 Jul 24.
citation: Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Shimizu M, Shobu Y, Kikuchi M. The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials. BMC Nephrol. 2016 Sep 30;17(1):141. doi: 10.1186/s12882-016-0357-9.