UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Japan Erythropoietin Treatment-Strvey for starting hemoglobin level in renal anemia management
Title of the study (Brief title)	JET-STREAM
Region	Japan

Condition
Condition	Renalanemic CKD patients in non-dialysis
Classification by specialty	Medicine in general Nephrology Urology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The objectives of the survey is to investigate the impact on renal survival and renal function of different hemoglobin levels for initiating Epogin(Epoetin Beta) treatment in non-dialysis CKD patients with renal anemia.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Renal events: Event days will be considered the days when the earliest of the following occurs. Individual events will also be analyzed. The date on which hemoglobin levels reach a certain value (e.g., 10 g/dL) instead of the first day of Epogin injection use will be employed as the beginning date to be used in evaluation. 1)Renal replacement therapy 2)Doubling time of creatinine level 3)eGFR<6.0 mL/min/1.73 m2
Key secondary outcomes	(1)Endpoints related to renal function Changes over time in hemoglobin levels, eGFR (rate of change, percentage of baseline eGFR), 1/Cr, and urinary protein and creatinine during the survey will be evaluated along with the relationships of these endpoints to patient background characteristics and event onset. (2)Cardiovascular disease events Event days will be considered the day of hospitalization or death due to any of the following cardiovascular diseases. heart failure, angina pectoris, myocardial infarction, cerebral infarction, cerebral hemorrhage, transient ischemic attack

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	(1)Patients to register: All non-dialysis CKD patients naive to erythropoiesis stimulating agent (ESA) therapy scheduled to start anemia treatment with Epogin Injection who will not likely introduce renal replacement therapy for at least six months and who could get informed consent to participate in the present survey. (2)Patients for whom a survey form is to be collected: All registered patients who use Epogin
Key exclusion criteria	The following patients will be excluded: 1)Patients with anemia caused by a condition other than renal anemia 2)Patients whose eGFR is less than 6 mL/min/1.73m2
Target sample size	2000

Research contact person
Name of lead principal investigator	JOJI MOCHIZUKI
Organization	CHUGAI PHARMACEUTICAL CO.,LTD.
Division name	DRUG SAFETY DEPT.
Address	1-1 NIHONBASHI-MUROMACHI 2-CHOME,CHUO-KU TOKYO,103-8324 JAPAN
TEL	03-3273-0769
Email	mochizukijuj@chugai-pharm.co.jp

Public contact
Name of contact person	IZUMI KAWASHIMA
Organization	CHUGAI PHARMACEUTICAL CO.,LTD.
Division name	PHARMACOVIGILANCE DEPT.
Address	PHARMACOVIGILANCE DEPT.
TEL	03-3273-0769
Homepage URL
Email	kawashimaizm@chugai-pharm.co.jp

Sponsor
Institute	CHUGAI PHARMACEUTICAL CO.,LTD.
Institute
Department

Funding Source
Organization	CHUGAI PHARMACEUTICAL CO.,LTD.
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2010 Year 02 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2009 Year 11 Month 12 Day
Anticipated trial start date	2010 Year 02 Month 01 Day
Last follow-up date	2013 Year 06 Month 30 Day
Date of closure to data entry	2013 Year 07 Month 01 Day
Date trial data considered complete	2013 Year 11 Month 14 Day
Date analysis concluded	2014 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://rd.springer.com/article/10.1007/s10157-015-1225-9
Results	In this prospective, multi-center, observational study, non-dialysis CKD patients with anemia who were naive to erythropoiesis-stimulating agents (ESAs) were divided into 3 groups based on their Hb levels at initiation of epoetin beta therapy (Group I: 10 <= Hb < 11 g/dL, Group II: 9 <= Hb < 10 g/dL, and Group III: Hb < 9 g/dL). The primary endpoint was time to first occurrence of any renal event. For the primary analysis, an inverse probability weighted Cox regression model was used to adjust time-dependent selection bias in the artificially censored data. A total of 1113 patients were eligible for primary endpoint analysis. Risk of renal events was significantly higher in Group III compared with Group I (HR, 2.52; 95% CI, 1.98 to 3.21; P < 0.0001); although not significant, the risk was also higher in Group II compared with Group I (HR, 1.48; 95% CI, 0.91 to 2.40; P = 0.11). Initiation of ESA therapy when Hb levels decreased below 11 g/dL but not below 10 g/dL could be more effective at reducing the risk of renal events in non-dialysis CKD patients with anemia compared with initiation of ESA therapy at below 9 g/dL or even 10 g/dL.
Other related information	(1)Analysis population The analysis population will consist of all patients fulfilling the registration criteria and for whom a survey form is collected provided the survey form indicates that Epogin was received at least once. An advisory committee will review and resolve any questions regarding patient handling (e.g., acceptance/rejection, inclusion in analysis population). (2)Analyses and analytical methods 1)The effects of baseline hemoglobin levels on events will be evaluated. Given the likely presence of multiple groups (regimens) according to baseline hemoglobin levels, inverse probability weighting or another appropriate method will be used to estimate hazard ratios. The times to renal replacement therapy, doubling of creatinine, and eGFR<6.0 mL/min/1.73 m2 will be individually evaluated, as will the times to halving of eGRF<7.0 mL/min/1.73 m2, creatinine 6.0 mg/dL or more, and creatinine 8.0 mg/dL or more. 2)A statistical method similar to that used in "1)" will be used to evaluate the relationship between baseline hemoglobin levels and hospitalization events and deaths attributable to cardiovascular disease (i.e., cardiac failure, angina pectoris, myocardial infarction, cerebral infarction, cerebral hemorrhage, transient ischemic attack). 3)Cox regression will be used to evaluate factors impacting event occurrence. 4)Changes over time in hemoglobin levels, eGFR (rate of change, percentage of baseline eGFR), 1/Cr, and urinary protein and creatinine during the survey will be plotted on graphs and otherwise evaluated along with the relationships of these endpoints to patient background characteristics and event onset.

Management information
Registered date	2010 Year 01 Month 29 Day
Last modified on	2018 Year 10 Month 17 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000003780