Comparing Efficacy and Safety of CinnaGen Beta Erythropoi... | NCT03408639

ID	Type	Description	Link
IRCT201601156135N6	Other Identifier	Food And Drug Administration of The Islamic Republic of Iran

Status Module

Description Module

Detailed Description

This study is a phase III, randomized, two-armed, parallel, double-blind (patient and assessor blinded), active-controlled noninferiority clinical trial to determine the non-inferior therapeutic efficacy and safety between CinnaPoietin® (Beta erythropoietin) and Eprex® (epoetin alpha) on the treatment of anemia in ESRD patient under hemodialysis. After signing the written informed consents, 156 patients have been planned to randomize and assign to receive CinnaPoietin® or Eprex® for a 26-weeks period. Administration dose for patients who are treated with erythropoietin is the similar dose of the previously administered amount (IV or SC without any change). After then, dose adjustment will be made based on patients' response. In addition to main intervention, Nephrovit tablet/day and B12 100 mcg/month were prescribed for patients. The primary objective of this study is to compare the efficacy of CinnaPoietin® with Eprex®. The secondary objectives of this study are further comparison and evaluation of efficacy and safety.

The clinical trial will be conducted according to the GCP considerations. A comprehensive validation check program is used to verify the data, and discrepancy reports are generated accordingly for resolution by the investigator.

In order to ensure the use of standard and unified procedure of each test, monitoring of each site and laboratory site are going to be applied by sponsor monitoring team and CRO as external monitoring team.

The same prefilled syringe is used for CinnaPoietin® to be sure that there is no difference between CinnaPoietin® and Eprex® as brand drug. The drugs will be relabeled, and the same label is used for both prefilled syringe. So neither investigators nor subjects are able to notice any differences between them and are blind to the assignment.

Determination of sample size 156 patients will be equally (1:1) divided into intervention arms (78 in each group considering drop out) for achieving 80% power in order to determine non-inferiority using a one-sided, independent sample t-test. The margin of non-inferiority is -1.00.

The true difference between the means is assumed to be -0.500. The significance level (alpha) of the test is 0.05. The data are drawn from populations with standard deviations of 1.200 and 1.200.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CinnaPoietin®	Experimental	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients.	Drug: CinnaPoietin® Drug: Nephrovit Drug: Vitamin B12 Injection
Eprex®	Active Comparator	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients.	Drug: Eprex® Drug: Nephrovit Drug: Vitamin B12 Injection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CinnaPoietin®	Drug	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Hb Change Level During the Last Four Weeks of Treatment	The primary endpoints of this study is to assess mean Hb change level during the last four weeks of treatment.	Week 22 to week 26
Mean Weekly Epoetin Dosage Per kg Body Weight During the Last Four Weeks of Treatment	The mean weekly epoetin dosage per kg body weight during the last four weeks of treatment necessary to maintain the Hb level within 10-12 g/dl during the last four weeks of treatment is considered as the second primary endpoint.	Week 22 to week 26

Secondary Outcomes

Measure	Description	Time Frame
The Proportion of Patients With Any Permanent or Transient Dose Change	The proportion of patients with any permanent or transient dose change during 26 weeks.	26 weeks
The Proportion of Patients With Any Hb Measurement Outside the Target Range (10-12 g/dl)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Aged between 18 and 70
ESRD patients who are on hemodialysis for ≥3 months.
Hb level 8- 11.5 g/dl
Patients are on adequate hemodialysis: the minimally adequate dose of hemodialysis given 3 times per week should be a spKt/V (single-pool delivered Kt/V; clearance of urea x dialysis time/volume of distribution) of 1.2 per dialysis. For treatment periods of less than 5 hours, an alternative minimum dose is a urea reduction rate (URR) of 65%. All types of hemodialysis systems and hemodiafiltration, including high-flux membranes are allowed as long as there is no plan to change the patient's regimen during the study.
Sufficient iron stores, defined as serum ferritin ≥ 200 ng/ml and transferrin saturation ≥20%. (Patients not meeting these criteria may receive iron supplementation therapy during the Screening and stabilization period to appropriately correct their iron store deficiency to meet the criterion required for randomization);
Ability to comply with study medication use, study visits, and study procedures as judged by the investigator;
Females of childbearing potential agree to use an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the duration of the study.
Qualified and willing to sign the informed consent form with the commitment of complying with all the scheduled visits, and study procedures as judged by the investigator;
In any circumstances that potential participants are not able to give consent, it may be given by responsible parents or guardian.

Exclusion Criteria:

Uncontrolled hypertension (defined as pre-dialysis diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥180 mmHg);
Anemia secondary to other causes different to the CKD (e.g. multiple myeloma, aplastic anemia, leukemia;….)
Decompensated liver failure;
Clinical evidence of concurrent uncontrolled hyperparathyroidism (defined as serum parathyroid hormone (iPTH) > 800 pg/ml);
Heart failure [New York Heart Association (NYHA) class III and IV];
Unstable angina pectoris, active cardiac disease, stroke and/or cardiac infarction within the last 6 months;
History of or active blood coagulation disorders including DVT, PTE, native access Thrombosis during last 6 months.
Thrombocytosis (platelet count > 500,000/µl);
Thrombocytopenia (platelet count < 100,000/µl);
White blood cell count < 3,000/µl);
White blood cell count >15,000/µl)
Recent Bleeding (acute or chronic bleeding within three months prior to screening);
Suspicion of or confirmed occult bleeding (increased reticulocyte count);
Clinical evidence of concurrent systemic infection, or inflammatory disease (e.g; diabetic foot, bed sore, access infection, CRP> 30 mg/l,…)
Currently receiving treatment for epilepsy;
Major surgery within 3 months prior to randomization and during the conduct of the trial (except vascular access surgery);
Concomitant immunosuppressive therapy; patients on a short course of steroids (up to 7 days), topical or intranasal steroids are allowed in the study;
History of any malignant disease within the last 5 years (except excised non-melanoma skin cancer);
Women who are pregnant or breastfeeding;
Known history of severe drug-related allergies;
Known history of drug related allergy to Erythropoietin or one of the ingredients of the test or the reference products or hypersensitivity to mammalian-derived products;
Transplant received within one year prior to the start of the study;
Simultaneous participation in another clinical study or having received an Investigational Medicinal Product within three months before randomization in this study.
Psychiatric, addictive (drugs or alcohol) or any other disorder that compromises the ability to give an informed consent;
Any red blood cell transfusion during the last 3 months (measured at the time of eligibility verification);
Primary hematological disorder (e.g. myelodysplastic syndrome, myeloma, sickle cell anemia, hematological malignancy, multiple myeloma hemolytic anemia);
known resistance to the rHuEPO defined by a requirement > 450 IU/kg/week by IV or 300 IU/kg/week by SC, equivalent to approximately 20.000 IU/week SC and in absence of iron deficiency;
who have suffered an event of active bleeding in the 30 days prior to the beginning of the study;
Morbid obesity, defined by a Body Mass Index (BMI) > 37 kg/m2 in women and > 40 kg/m2 in men.

Facility	Status	City	State	ZIP	Country	Contacts
Javad-al-Aemeh clinic		Kerman			Iran
SHAFA Hospital

PubMed Identifier	Type	Citation	Retractions
12076240	Background	Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2002 Jun 24;162(12):1401-8. doi: 10.1001/archinte.162.12.1401.
18498676	Background	McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009 Apr;12(4):444-54. doi: 10.1017/S1368980008002401. Epub 2008 May 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 23, 2015	Sep 2, 2019

Arm/Group Information

ID	Title	Description
BG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
BG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00055.02± 11.38 BG00150.01± 12.72 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00033 BG00133 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Iran

Title	Measurements
	BG00078 BG00178 BG002

Hemoglobin concentration

Mean

Standard Deviation

g/dL

Title

Denominators

Categories

Title	Measurements
	BG00010.41± 0.89 BG00110.64± 0.82 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Hb Change Level During the Last Four Weeks of Treatment

The primary endpoints of this study is to assess mean Hb change level during the last four weeks of treatment.

Posted

Mean

Standard Deviation

g/dL

Week 22 to week 26

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Units	Counts
Participants	OG00061 OG00138

Title

Denominators

Categories

Title	Measurements
	OG0000.4± 1.26 OG0010.74± 1.39

Primary

Mean Weekly Epoetin Dosage Per kg Body Weight During the Last Four Weeks of Treatment

The mean weekly epoetin dosage per kg body weight during the last four weeks of treatment necessary to maintain the Hb level within 10-12 g/dl during the last four weeks of treatment is considered as the second primary endpoint.

Posted

Mean

Standard Deviation

IU/Kg/week

Week 22 to week 26

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients With Any Permanent or Transient Dose Change

The proportion of patients with any permanent or transient dose change during 26 weeks.

Posted

Number

proportion of patients

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients With Any Hb Measurement Outside the Target Range (10-12 g/dl)

The proportion of patients with any Hb measurement outside the target range (10-12 g/dl) during 26 weeks.

Posted

Number

proportion of patients

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients Needed Blood Transfusions

The proportion of patients needed blood transfusions during 26 weeks.

Posted

Number

proportion of patients

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients With Treatment Success

Treatment success is considered as Hb concentration equal to or more than 11.0 g/dl and two consecutive weeks without any blood transfusion within the preceding three months

Posted

Number

proportion of patients

Week 12 to week 26

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients With Maintenance Success

Maintenance success is considered as maintenance success is considered as maintenance of mean Hb concentration of 11.0 ± 1.0 g/dl for at least four consecutive weeks

Posted

Number

proportion of patients

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Percentage of Patients With Hb Measurements More Than 10.0 g/dl

The percentage of patients with Hb measurements more than 10.0 g/dl from week 22 to week 26.

Posted

Count of Participants

Participants

Week 22 to week 26

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Percentage of Patients With Hematocrit Measurements More Than 30%

The percentage of patients with hematocrit measurements more than 30% from week 22 to week 26.

Posted

Number

percentage of patients

Week 22 to week 26

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Incidence of Hb Levels Above 13 g/dl

The first safety endpoint is the proportion of patients with at least one Hb measurement above 13 g/dL.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Proportion of Patients With an Increase in Hb Concentration of > 1.0 g/dl for Four Consecutive Weeks

The proportion of patients with an increase in Hb concentration of > 1.0 g/dl for four consecutive weeks during 26 weeks.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Secondary

The Incidence of Adverse Events

The incidence of adverse events during 26 weeks.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.
OG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CinnaPoietin®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. CinnaPoietin®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.	5	78	14	78	11	78
EG001	Eprex®	The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. In addition to main intervention, Nephrovit tablet/day and vitamine B12 100 mcg/month will be prescribed for patients. Eprex®: The starting dose of Erythropoietin is 60 (50-100) IU/kg body weight/week for naïve patients. Administration dose for patients who are treated with erythropoietin is similar dose of previously administered amount (IV or SC without any change). After then, dose adjustment will be done based on patients' response. Nephrovit: Nephrovit tablet is daily administered to all the patients. Vitamin B12 Injection: Vitamin B12 is monthly injected to all the patients.	5	78	7	78	12	78

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Palpitation, Cardiac Function Impairment, Cardiac Infraction, Chest Pain, Tachycardia)	Cardiac disorders	Systematic Assessment	EG0002 affected78 at risk EG0013 affected78 at risk
Inflation on Ankle	Renal and urinary disorders	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk
(Skin reaction, Catheter defect, Disability catheter, Filter clots, pain in injection site, skin rea	General disorders	Systematic Assessment	EG0004 affected78 at risk EG0010 affected78 at risk
Gallstones	Hepatobiliary disorders	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk
(Pneumonia, Infection of right hand Lower than the fistula)	Infections and infestations	Systematic Assessment	EG0002 affected78 at risk EG0010 affected78 at risk
(CO toxicity, transplantation complication)	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected78 at risk EG0012 affected78 at risk
(tearing of tendon in both knees, back pain, Musculoskeletal-Bone pain, knee tenderness due to joint	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected78 at risk EG0011 affected78 at risk
(Respiratory disorder, chest pain and dyspenea, dyspnea)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk
echymosis due to recent car accident, itching)	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
Cardiac pacemaker AND Valve Replacement, orthopedic surgery)	Surgical and medical procedures	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
(Eosinophilia, Thrombocytopenia)	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
(Palpitation, Cardiac Function Impairment, Cardiac Infraction, Chest Pain, Tachycardia)	Cardiac disorders	Systematic Assessment	EG0001 affected78 at risk EG0013 affected78 at risk
(Skin reaction, Catheter defect, Disability catheter, Filter clots, pain in injection site, skin rea	General disorders	Systematic Assessment	EG0003 affected78 at risk EG0011 affected78 at risk
(Pneumonia, Infection of right hand Lower than the fistula)	Infections and infestations	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
(tearing of tendon in both knees, back pain, Musculoskeletal-Bone pain, knee tenderness due to joint	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
(numbness in the wrist, dizziness)	Nervous system disorders	Systematic Assessment	EG0001 affected78 at risk EG0011 affected78 at risk
Decreased libido	Psychiatric disorders	Systematic Assessment	EG0001 affected78 at risk EG0010 affected78 at risk
vaginal discharge	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
(Respiratory disorder, chest pain and dyspenea, dyspnea)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected78 at risk EG0010 affected78 at risk
(itching, echymosis due to recent car accident, itching)	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected78 at risk EG0012 affected78 at risk
(Installing Cardiac pacemaker AND Valve Replacement, orthopedic surgery)	Surgical and medical procedures	Systematic Assessment	EG0000 affected78 at risk EG0011 affected78 at risk
(blood clotting, Bleeding catheter, Hemorrage, Vascular disorders)	Vascular disorders	Systematic Assessment	EG0002 affected78 at risk EG0010 affected78 at risk

ID	Term
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D000068817	Epoetin Alfa
D014805	Vitamin B 12

ID	Term
D004921	Erythropoietin
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D045728	Corrinoids
D045725	Tetrapyrroles
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds