UMIN-CTR Clinical Trial

Public title

Japan Erythropoietin Treatment-Strvey for starting hemoglobin level in renal anemia management

Acronym

JET-STREAM

Scientific Title

Japan Erythropoietin Treatment-Strvey for starting hemoglobin level in renal anemia management

Scientific Title:Acronym

JET-STREAM

Region

Japan

Condition

Renalanemic CKD patients in non-dialysis

Classification by specialty

Medicine in general	Nephrology	Urology

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	JOJI MOCHIZUKI

Organization

CHUGAI PHARMACEUTICAL CO.,LTD.

Division name

DRUG SAFETY DEPT.

Zip code

Address

1-1 NIHONBASHI-MUROMACHI 2-CHOME,CHUO-KU TOKYO,103-8324 JAPAN

TEL

03-3273-0769

Email

mochizukijuj@chugai-pharm.co.jp

Name of contact person

1st name
Middle name
Last name	IZUMI KAWASHIMA

Organization

CHUGAI PHARMACEUTICAL CO.,LTD.

Division name

PHARMACOVIGILANCE DEPT.

Zip code

Address

PHARMACOVIGILANCE DEPT.

TEL

03-3273-0769

Homepage URL

Email

kawashimaizm@chugai-pharm.co.jp

Institute

CHUGAI PHARMACEUTICAL CO.,LTD.

Institute

Department

Personal name

Organization

CHUGAI PHARMACEUTICAL CO.,LTD.

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2010

Year

02

Month

01

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://rd.springer.com/article/10.1007/s10157-015-1225-9

Number of participants that the trial has enrolled

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.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2009

Year

11

Month

12

Day

Date of IRB

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

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.

Registered date

2010

Year

01

Month

29

Day

Last modified on

2018

Year

10

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003780