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A Phase 3b Study of Erythropoietin Drugs Using a Specified Dosing Algorithm in Patients With Chronic Kidney Disease on Hemodialysis

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ClinicalTrials.gov Identifier: NCT02504294
Recruitment Status : Completed
First Posted : July 21, 2015
Results First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Sponsor:
Collaborator:
Hospira, now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Chronic Kidney Disease (CKD)
Interventions Biological: Epoetin Hospira Arm
Other: Standard of Care Arm
Drug: IV Iron
Enrollment 432
Recruitment Details  
Pre-assignment Details In this study, 432 participants were enrolled, however, only 418 participants were treated.
Arm/Group Title Epoetin Hospira Epogen
Hide Arm/Group Description Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
Period Title: Overall Study
Started 212 206
Completed 156 158
Not Completed 56 48
Reason Not Completed
Adverse Event             15             12
Withdrawal by Subject             7             1
Protocol Violation             27             26
Physician Decision             1             2
Lost to Follow-up             6             7
Arm/Group Title Epoetin Hospira Epogen Total
Hide Arm/Group Description Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. Total of all reporting groups
Overall Number of Baseline Participants 212 206 418
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all participants who received at least 1 dose of study medication after randomization into the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 212 participants 206 participants 418 participants
60.5  (13.96) 59.3  (14.23) 59.9  (14.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 212 participants 206 participants 418 participants
Female
82
  38.7%
102
  49.5%
184
  44.0%
Male
130
  61.3%
104
  50.5%
234
  56.0%
1.Primary Outcome
Title Percentage of Time When Participants Had Hemoglobin Levels Between 9 to 11 Gram Per Deciliter (g/dL)
Hide Description [Not Specified]
Time Frame Week 17 up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of study medication after randomization into the study. Here, "Number of participants analyzed (N)" signifies those number of participants who were evaluable for this outcome measure.
Arm/Group Title Epoetin Hospira Epogen
Hide Arm/Group Description:
Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
Overall Number of Participants Analyzed 178 173
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Weeks
61.9330
(57.5106 to 66.1659)
63.3305
(58.7061 to 67.7217)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Epoetin Hospira, Epogen
Comments Clustered binomial analysis using logistic regression method was performed and generalized estimating equation method was used to construct 95 percent (%) two-sided confidence intervals (CIs).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was concluded since the lower bound of the 95% CI of the difference in percentage was greater than the non-inferiority margin (-12.5%).
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -1.3975
Confidence Interval (2-Sided) 95%
-7.6503 to 4.8553
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Weekly Mean Study Medication Dose Over Final 8 Weeks of Study Treatment
Hide Description [Not Specified]
Time Frame Baseline (8 Weeks prior to randomization), Week 17 up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of study medication after randomization in to the study. Here, "N" signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Epoetin Hospira Epogen
Hide Arm/Group Description:
Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
Overall Number of Participants Analyzed 180 174
Least Squares Mean (Standard Error)
Unit of Measure: Units per week
-1861.8  (563.50) -799.8  (573.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Epoetin Hospira, Epogen
Comments P-value was calculated using analysis of covariance (ANCOVA) model with treatment as factor and baseline ESA dose as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1874
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1062.0
Confidence Interval (2-Sided) 95%
-2643.2 to 519.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 803.95
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study.
 
Arm/Group Title Epoetin Hospira Epogen
Hide Arm/Group Description Participants received intravenous (IV) injection of Epoetin Hospira as per the analogous version of Fresenius Medical Care North America (FMCNA) Erythropoietin Stimulating Agent (ESA) dosing algorithm Corporate Medical Advisory board (cMAB algorithm 1) along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26. Participants received their ongoing standard of care which included IV injection of Epogen, as per the current version of the FMCNA ESA dosing algorithm cMAB 5 along with IV iron as per the FMCNA standard of care. Drug was administered up to maximum 3 times per week up to Week 24. Participants were followed up to Week 26.
All-Cause Mortality
Epoetin Hospira Epogen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Epoetin Hospira Epogen
Affected / at Risk (%) Affected / at Risk (%)
Total   66/212 (31.13%)   64/206 (31.07%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/212 (0.47%)  2/206 (0.97%) 
Haemorrhagic anaemia * 1  0/212 (0.00%)  1/206 (0.49%) 
Cardiac disorders     
Acute myocardial infarction * 1  2/212 (0.94%)  2/206 (0.97%) 
Angina pectoris * 1  0/212 (0.00%)  1/206 (0.49%) 
Angina unstable * 1  1/212 (0.47%)  0/206 (0.00%) 
Atrial fibrillation * 1  1/212 (0.47%)  0/206 (0.00%) 
Atrial flutter * 1  1/212 (0.47%)  0/206 (0.00%) 
Bradycardia * 1  1/212 (0.47%)  0/206 (0.00%) 
Cardiac arrest * 1  2/212 (0.94%)  6/206 (2.91%) 
Cardiac failure congestive * 1  0/212 (0.00%)  3/206 (1.46%) 
Cardio-respiratory arrest * 1  0/212 (0.00%)  2/206 (0.97%) 
Coronary artery disease * 1  0/212 (0.00%)  2/206 (0.97%) 
Diastolic dysfunction * 1  0/212 (0.00%)  1/206 (0.49%) 
Hypertensive heart disease * 1  1/212 (0.47%)  0/206 (0.00%) 
Myocardial infarction * 1  1/212 (0.47%)  0/206 (0.00%) 
Ventricular tachycardia * 1  1/212 (0.47%)  0/206 (0.00%) 
Endocrine disorders     
Hyperparathyroidism secondary * 1  1/212 (0.47%)  0/206 (0.00%) 
Parathyroid disorder * 1  0/212 (0.00%)  1/206 (0.49%) 
Gastrointestinal disorders     
Abdominal distension * 1  1/212 (0.47%)  0/206 (0.00%) 
Abdominal pain * 1  1/212 (0.47%)  0/206 (0.00%) 
Abdominal pain lower * 1  0/212 (0.00%)  1/206 (0.49%) 
Gastrointestinal haemorrhage * 1  2/212 (0.94%)  1/206 (0.49%) 
Impaired gastric emptying * 1  0/212 (0.00%)  1/206 (0.49%) 
Large intestine perforation * 1  0/212 (0.00%)  1/206 (0.49%) 
Lower gastrointestinal haemorrhage * 1  0/212 (0.00%)  1/206 (0.49%) 
Nausea * 1  1/212 (0.47%)  2/206 (0.97%) 
Upper gastrointestinal haemorrhage * 1  1/212 (0.47%)  0/206 (0.00%) 
Vomiting * 1  1/212 (0.47%)  2/206 (0.97%) 
General disorders     
Asthenia * 1  0/212 (0.00%)  1/206 (0.49%) 
Catheter site haemorrhage * 1  0/212 (0.00%)  1/206 (0.49%) 
Chest discomfort * 1  1/212 (0.47%)  0/206 (0.00%) 
Chest pain * 1  3/212 (1.42%)  1/206 (0.49%) 
Condition aggravated * 1  4/212 (1.89%)  3/206 (1.46%) 
Death * 1  2/212 (0.94%)  0/206 (0.00%) 
Early satiety * 1  1/212 (0.47%)  0/206 (0.00%) 
Generalised oedema * 1  0/212 (0.00%)  1/206 (0.49%) 
Hernia * 1  0/212 (0.00%)  1/206 (0.49%) 
Impaired healing * 1  0/212 (0.00%)  2/206 (0.97%) 
Medical device site ulcer * 1  0/212 (0.00%)  1/206 (0.49%) 
Pain * 1  1/212 (0.47%)  0/206 (0.00%) 
Pyrexia * 1  0/212 (0.00%)  1/206 (0.49%) 
Systemic inflammatory response syndrome * 1  0/212 (0.00%)  1/206 (0.49%) 
Ulcer haemorrhage * 1  0/212 (0.00%)  1/206 (0.49%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  1/212 (0.47%)  0/206 (0.00%) 
Cholelithiasis * 1  1/212 (0.47%)  0/206 (0.00%) 
Infections and infestations     
Bacteraemia * 1  1/212 (0.47%)  0/206 (0.00%) 
Cellulitis * 1  0/212 (0.00%)  1/206 (0.49%) 
Cellulitis of male external genital organ * 1 [1]  0/130 (0.00%)  1/104 (0.96%) 
Clostridium difficile colitis * 1  1/212 (0.47%)  0/206 (0.00%) 
Device related sepsis * 1  1/212 (0.47%)  0/206 (0.00%) 
Diverticulitis * 1  0/212 (0.00%)  1/206 (0.49%) 
Endocarditis * 1  1/212 (0.47%)  0/206 (0.00%) 
Escherichia bacteraemia * 1  1/212 (0.47%)  0/206 (0.00%) 
Gastroenteritis * 1  2/212 (0.94%)  1/206 (0.49%) 
Graft infection * 1  1/212 (0.47%)  0/206 (0.00%) 
Incision site infection * 1  1/212 (0.47%)  0/206 (0.00%) 
Infection * 1  2/212 (0.94%)  0/206 (0.00%) 
Osteomyelitis * 1  0/212 (0.00%)  2/206 (0.97%) 
Osteomyelitis chronic * 1  1/212 (0.47%)  0/206 (0.00%) 
Pneumonia * 1  7/212 (3.30%)  1/206 (0.49%) 
Pneumonia bacterial * 1  1/212 (0.47%)  0/206 (0.00%) 
Pyelonephritis * 1  2/212 (0.94%)  0/206 (0.00%) 
Pyuria * 1  1/212 (0.47%)  0/206 (0.00%) 
Respiratory syncytial virus infection * 1  0/212 (0.00%)  1/206 (0.49%) 
Sepsis * 1  3/212 (1.42%)  1/206 (0.49%) 
Septic shock * 1  2/212 (0.94%)  1/206 (0.49%) 
Subcutaneous abscess * 1  0/212 (0.00%)  1/206 (0.49%) 
Urinary tract infection * 1  2/212 (0.94%)  2/206 (0.97%) 
Wound infection * 1  0/212 (0.00%)  1/206 (0.49%) 
Injury, poisoning and procedural complications     
Arteriovenous fistula site haemorrhage * 1  1/212 (0.47%)  2/206 (0.97%) 
Arteriovenous fistula thrombosis * 1  1/212 (0.47%)  0/206 (0.00%) 
Arteriovenous graft site haemorrhage * 1  1/212 (0.47%)  1/206 (0.49%) 
Arteriovenous graft thrombosis * 1  1/212 (0.47%)  1/206 (0.49%) 
Fall * 1  0/212 (0.00%)  1/206 (0.49%) 
Femur fracture * 1  0/212 (0.00%)  1/206 (0.49%) 
Intentional product misuse * 1  1/212 (0.47%)  0/206 (0.00%) 
Limb injury * 1  0/212 (0.00%)  1/206 (0.49%) 
Post procedural pulmonary embolism * 1  0/212 (0.00%)  1/206 (0.49%) 
Pubis fracture * 1  0/212 (0.00%)  1/206 (0.49%) 
Rib fracture * 1  0/212 (0.00%)  1/206 (0.49%) 
Tibia fracture * 1  1/212 (0.47%)  1/206 (0.49%) 
Vascular access complication * 1  0/212 (0.00%)  2/206 (0.97%) 
Vascular access malfunction * 1  0/212 (0.00%)  1/206 (0.49%) 
Vascular bypass dysfunction * 1  1/212 (0.47%)  0/206 (0.00%) 
Vascular pseudoaneurysm * 1  1/212 (0.47%)  0/206 (0.00%) 
Wound * 1  1/212 (0.47%)  0/206 (0.00%) 
Wound dehiscence * 1  0/212 (0.00%)  1/206 (0.49%) 
Investigations     
Haemoglobin decreased * 1  1/212 (0.47%)  0/206 (0.00%) 
Metabolism and nutrition disorders     
Diabetic ketoacidosis * 1  0/212 (0.00%)  1/206 (0.49%) 
Failure to thrive * 1  1/212 (0.47%)  0/206 (0.00%) 
Fluid overload * 1  4/212 (1.89%)  3/206 (1.46%) 
Hyperglycaemia * 1  0/212 (0.00%)  1/206 (0.49%) 
Hyperkalaemia * 1  5/212 (2.36%)  1/206 (0.49%) 
Hypoglycaemia * 1  1/212 (0.47%)  1/206 (0.49%) 
Hypovolaemia * 1  0/212 (0.00%)  1/206 (0.49%) 
Malnutrition * 1  0/212 (0.00%)  1/206 (0.49%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness * 1  1/212 (0.47%)  0/206 (0.00%) 
Pain in extremity * 1  1/212 (0.47%)  0/206 (0.00%) 
Systemic lupus erythematosus * 1  0/212 (0.00%)  1/206 (0.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung carcinoma cell type unspecified stage IV * 1  1/212 (0.47%)  0/206 (0.00%) 
Prostate cancer * 1 [1]  1/130 (0.77%)  0/104 (0.00%) 
Nervous system disorders     
Cerebrovascular accident * 1  2/212 (0.94%)  1/206 (0.49%) 
Encephalopathy * 1  1/212 (0.47%)  2/206 (0.97%) 
Hemiparesis * 1  0/212 (0.00%)  1/206 (0.49%) 
Ischaemic stroke * 1  0/212 (0.00%)  1/206 (0.49%) 
Lethargy * 1  0/212 (0.00%)  1/206 (0.49%) 
Metabolic encephalopathy * 1  2/212 (0.94%)  0/206 (0.00%) 
Syncope * 1  2/212 (0.94%)  0/206 (0.00%) 
Transient ischaemic attack * 1  0/212 (0.00%)  1/206 (0.49%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1 [1]  0/82 (0.00%)  1/102 (0.98%) 
Psychiatric disorders     
Anxiety * 1  1/212 (0.47%)  0/206 (0.00%) 
Major depression * 1  1/212 (0.47%)  0/206 (0.00%) 
Renal and urinary disorders     
Obstructive uropathy * 1  1/212 (0.47%)  0/206 (0.00%) 
Urethral haemorrhage * 1  0/212 (0.00%)  1/206 (0.49%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema * 1  1/212 (0.47%)  1/206 (0.49%) 
Acute respiratory failure * 1  2/212 (0.94%)  2/206 (0.97%) 
Asthma * 1  0/212 (0.00%)  1/206 (0.49%) 
Bronchial secretion retention * 1  1/212 (0.47%)  0/206 (0.00%) 
Choking * 1  1/212 (0.47%)  0/206 (0.00%) 
Chronic obstructive pulmonary disease * 1  2/212 (0.94%)  0/206 (0.00%) 
Dyspnoea * 1  2/212 (0.94%)  0/206 (0.00%) 
Hypoxia * 1  0/212 (0.00%)  2/206 (0.97%) 
Pleural effusion * 1  0/212 (0.00%)  2/206 (0.97%) 
Pulmonary oedema * 1  2/212 (0.94%)  2/206 (0.97%) 
Respiratory arrest * 1  0/212 (0.00%)  1/206 (0.49%) 
Respiratory failure * 1  1/212 (0.47%)  1/206 (0.49%) 
Tracheomalacia * 1  1/212 (0.47%)  0/206 (0.00%) 
Skin and subcutaneous tissue disorders     
Purpura * 1  1/212 (0.47%)  0/206 (0.00%) 
Surgical and medical procedures     
Renal transplant * 1  1/212 (0.47%)  1/206 (0.49%) 
Vascular disorders     
Hypertension * 1  0/212 (0.00%)  1/206 (0.49%) 
Hypertensive crisis * 1  1/212 (0.47%)  2/206 (0.97%) 
Hypotension * 1  0/212 (0.00%)  2/206 (0.97%) 
Peripheral artery occlusion * 1  0/212 (0.00%)  1/206 (0.49%) 
Steal syndrome * 1  0/212 (0.00%)  1/206 (0.49%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.0
[1]
This event was gender specific.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Epoetin Hospira Epogen
Affected / at Risk (%) Affected / at Risk (%)
Total   10/212 (4.72%)   21/206 (10.19%) 
Gastrointestinal disorders     
Nausea * 1  3/212 (1.42%)  13/206 (6.31%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  7/212 (3.30%)  11/206 (5.34%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer, Inc.
Organization: Pfizer ClinicalTrials.gov Call Center
Phone: 1--800--718--1021
EMail: ClinicalTrials.gov_Inquiries@Pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02504294    
Other Study ID Numbers: ZIN-EPO-1503
C3461008 ( Other Identifier: Alias Study Number )
First Submitted: July 20, 2015
First Posted: July 21, 2015
Results First Submitted: May 16, 2018
Results First Posted: June 13, 2018
Last Update Posted: June 13, 2018