Clinical trial NCT00501046: A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease Including Assessment of Quality of Life (EPPIC-2)
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 Including Assessment of Quality of Life
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: 1015
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 and quality of life.


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 obtained at Screening
* Blood pressure \<= 160/90 mmHg at both Screening and Baseline visits. 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, Early Term/Discontinuation (Mean: 430.293 Days), Final Visit (Mean: 908.486 Days)
measure: Vitamin B12 Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 425.112 Days), Final Visit (Mean: 910.988 Days)
measure: 25-Hydroxyvitamin D Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 429.695 Days), Final Visit (Mean: 908.601 Days)
measure: Vitamin E Levels
timeFrame: Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 427.067 Days), Final Visit (Mean: 908.715 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: 432.942 Days), Final Visit (Mean: 910.448 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: 420.569 Days), Final Visit (Mean: 909.848 Days)
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
state: Alabama
city: Hot Springs
country: United States
state: Arkansas
city: Bakersfield
country: United States
state: California
city: Glendale
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Riverside
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Boynton Beach
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Evergreen Park
country: United States
state: Illinois
city: Shawnee Mission
country: United States
state: Kansas
city: Kenner
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Pontiac
country: United States
state: Michigan
city: Brooklyn Center
country: United States
state: Minnesota
city: Flushing
country: United States
state: New York
city: Great Neck
country: United States
state: New York
city: New York
country: United States
state: New York
city: Williamsville
country: United States
state: New York
city: Elizabeth City
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Bend
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Doylestown
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Orangeburg
country: United States
state: South Carolina
city: Sumter
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Vancouver
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Tucumán
country: Argentina
city: Belo Horizonte
country: Brazil
city: Botucatu
country: Brazil
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Ibirapuera
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Sorocaba
country: Brazil
city: São Paulo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Hradec Kralove
country: Czechia
city: Liberec
country: Czechia
city: Praha
country: Czechia
city: Usti nad Labem
country: Czechia
city: Hamburg
country: Germany
city: Kiel
country: Germany
city: Mainz
country: Germany
city: Aguascalientes
country: Mexico
city: Cuernavaca
country: Mexico
city: Durango
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: Bialystok
country: Poland
city: Czestochowa
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: San Juan
country: Puerto Rico
city: Arkhangelsk
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Yaroslayl
country: Russian Federation
city: A Coruña
country: Spain
city: Asturias
country: Spain
city: Barcelona
country: Spain
city: Guadalajara
country: Spain
city: Madrid
country: Spain
city: Ivano-Frankivsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Lugansk
country: Ukraine
city: Lviv
country: Ukraine
city: Nikolaev
country: Ukraine
city: Poltava
country: Ukraine
city: Ternopol
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zaporizhzhya
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.