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A Trial Comparing Ferumoxytol to Iron Sucrose for the Treatment of Iron Deficiency Anemia in Adult Subjects With Chronic Kidney Disease (FIRST)

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ClinicalTrials.gov Identifier: NCT01052779
Recruitment Status : Completed
First Posted : January 20, 2010
Results First Posted : May 15, 2018
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
AMAG Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Iron Deficiency
Anemia
Kidney Disease
Interventions Drug: Ferumoxytol
Drug: Iron Sucrose
Enrollment 162
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ferumoxytol Iron Sucrose
Hide Arm/Group Description Participants received an intravenous (IV) injection of ferumoxytol (510 milligrams [mg], 17 milliliters [mL]) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 grams (g).

Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.

Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g.

Period Title: Overall Study
Started 80 82
Received at Least 1 Dose of Study Drug 80 81
Completed 75 73
Not Completed 5 9
Reason Not Completed
Adverse Event             1             4
Withdrawal by Subject             1             2
Other-Protocol Violation             1             1
Other-Surgery             0             2
Other-Missed Week 5 Visit             2             0
Arm/Group Title Ferumoxytol Iron Sucrose Total
Hide Arm/Group Description Participants received an IV injection of ferumoxytol (510 mg, 17 mL) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 g.

Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.

Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g.

Total of all reporting groups
Overall Number of Baseline Participants 80 82 162
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population: Any randomized participant who had any exposure to study drug (IV ferumoxytol or IV iron sucrose).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 80 participants 82 participants 162 participants
61.9  (15.00) 63.3  (15.16) 62.6  (15.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 82 participants 162 participants
Female
41
  51.2%
39
  47.6%
80
  49.4%
Male
39
  48.8%
43
  52.4%
82
  50.6%
Dialysis Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 82 participants 162 participants
Hemodialysis
34
  42.5%
36
  43.9%
70
  43.2%
Nondialysis
46
  57.5%
46
  56.1%
92
  56.8%
1.Primary Outcome
Title Mean Change In Hemoglobin From Baseline (Day 1) To Week 5
Hide Description

The change in hemoglobin from Baseline (Day 1) to Week 5 was calculated for each participant as:

Hemoglobin Change = Hemoglobin (Week 5) - Hemoglobin (Baseline)

The least squares mean, with standard error, is reported as g/deciliter (dL). Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug). The screening hemoglobin value was used for any participants with missing Baseline (Day 1) hemoglobin. Analysis used last observed carried forward (LOCF) imputation methods for missing values for the ITT population. Sensitivity analyses were performed without imputation for missing data and with the Markov chain Monte Carlo method.

Time Frame Baseline (Day 1), Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Any randomized participant who had any exposure to study drug (IV ferumoxytol or IV iron sucrose).
Arm/Group Title Ferumoxytol Iron Sucrose
Hide Arm/Group Description:
Participants received an IV injection of ferumoxytol (510 mg, 17 mL) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 g.

Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.

Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g.

Overall Number of Participants Analyzed 80 82
Least Squares Mean (Standard Error)
Unit of Measure: g/dL
With LOCF Imputation 0.84  (0.14) 0.74  (0.14)
Without Imputation (Sensitivity Analysis) 0.89  (0.15) 0.80  (0.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ferumoxytol, Iron Sucrose
Comments With LOCF Imputation: The p-value and two-sided 95% confidence interval (CI) for the treatment difference in mean change in hemoglobin from Baseline (Day 1) to Week 5 were generated based on an analysis of variance (ANOVA) model adjusted for baseline hemoglobin level and hemodialysis status.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was concluded if the lower bound of the 95% CI was ≥-0.5 g/dL and superiority if the lower bound was ≥0 g/dL.
Statistical Test of Hypothesis P-Value 0.515
Comments The p-value for hemoglobin change from Baseline (Day 1) was adjusted for baseline hemoglobin level and hemodialysis status.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.21 to 0.41
Estimation Comments The 95% CI for hemoglobin change from Baseline (Day 1) was from an ANOVA model and adjusted for baseline hemoglobin level and hemodialysis status.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ferumoxytol, Iron Sucrose
Comments Without Imputation (Sensitivity Analysis): The p-value and two-sided 95% CI for the treatment difference in mean change in hemoglobin from Baseline (Day 1) to Week 5 were generated based on an ANOVA model adjusted for baseline hemoglobin level and hemodialysis status.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was concluded if the lower bound of the 95% CI was ≥-0.5 g/dL and superiority if the lower bound was ≥0 g/dL.
Statistical Test of Hypothesis P-Value 0.587
Comments The p-value for hemoglobin change from Baseline (Day 1) was adjusted for baseline hemoglobin level and hemodialysis status.
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.23 to 0.41
Estimation Comments The 95% CI for hemoglobin change from Baseline (Day 1) was from an ANOVA model and adjusted for baseline hemoglobin level and hemodialysis status.
2.Primary Outcome
Title Percentage Of Participants With An Increase In Hemoglobin ≥1.0 g/dL From Day 1 (Baseline) To Week 5
Hide Description The percentage of participants who achieved a ≥1.0 g/dL increase in hemoglobin at any time from Baseline (Day 1) up to Week 5 by treatment group is presented by study visit. Baseline hemoglobin for each participant was the Day 1 hemoglobin value (prior to injection of the study drug).
Time Frame Baseline (Day 1) and up to Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Any randomized participant who had any exposure to study drug (IV ferumoxytol or IV iron sucrose).
Arm/Group Title Ferumoxytol Iron Sucrose
Hide Arm/Group Description:
Participants received an IV injection of ferumoxytol (510 mg, 17 mL) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 g.

Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.

Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g.

Overall Number of Participants Analyzed 80 82
Measure Type: Count of Participants
Unit of Measure: Participants
Week 2
20
  25.0%
11
  13.4%
Week 3
32
  40.0%
20
  24.4%
Week 4
37
  46.3%
31
  37.8%
Week 5
40
  50.0%
34
  41.5%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ferumoxytol Iron Sucrose
Hide Arm/Group Description Participants received an IV injection of ferumoxytol (510 mg, 17 mL) on Day 1 (Baseline). This was followed by a second injection of ferumoxytol (510 mg, 17 mL) 5±3 days later for a total cumulative dose of 1.02 g.

Participants received iron sucrose based on hemodialysis status. Participants on hemodialysis received either slow IV injection or IV drip infusion of 100 mg of iron sucrose on Day 1 (Baseline) and at the following 9 consecutive hemodialysis sessions for a total cumulative dose of 1.0 g.

Participants not on dialysis received either slow IV injection or IV drip infusion of 200 mg of iron sucrose on Day 1 (Baseline) and at 4 subsequent visits on nonconsecutive days over a 14-day period for a total cumulative dose of 1.0 g.

All-Cause Mortality
Ferumoxytol Iron Sucrose
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Ferumoxytol Iron Sucrose
Affected / at Risk (%) Affected / at Risk (%)
Total   7/80 (8.75%)   6/82 (7.32%) 
Gastrointestinal disorders     
Abdominal pain  1/80 (1.25%)  0/82 (0.00%) 
Peritoneal adhesions  1/80 (1.25%)  0/82 (0.00%) 
Small intestinal obstruction  1/80 (1.25%)  0/82 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1/80 (1.25%)  0/82 (0.00%) 
Infections and infestations     
Abscess limb  0/80 (0.00%)  1/82 (1.22%) 
Arteriovenous graft site infection  0/80 (0.00%)  1/82 (1.22%) 
Cellulitis  0/80 (0.00%)  1/82 (1.22%) 
Gastroenteritis  1/80 (1.25%)  0/82 (0.00%) 
Pneumonia  0/80 (0.00%)  1/82 (1.22%) 
Urinary tract infection  0/80 (0.00%)  1/82 (1.22%) 
Injury, poisoning and procedural complications     
Anastomotic haemorrhage  1/80 (1.25%)  0/82 (0.00%) 
Seroma  0/80 (0.00%)  1/82 (1.22%) 
Vascular graft thrombosis  0/80 (0.00%)  1/82 (1.22%) 
Metabolism and nutrition disorders     
Hyperkalaemia  0/80 (0.00%)  1/82 (1.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm  0/80 (0.00%)  1/82 (1.22%) 
Renal and urinary disorders     
Acute prerenal failure  1/80 (1.25%)  0/82 (0.00%) 
Renal failure chronic  0/80 (0.00%)  1/82 (1.22%) 
Vascular disorders     
Deep vein thrombosis  1/80 (1.25%)  0/82 (0.00%) 
Hypotension  0/80 (0.00%)  1/82 (1.22%) 
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Ferumoxytol Iron Sucrose
Affected / at Risk (%) Affected / at Risk (%)
Total   35/80 (43.75%)   50/82 (60.98%) 
Blood and lymphatic system disorders     
Anaemia  2/80 (2.50%)  1/82 (1.22%) 
Iron deficiency anaemia  0/80 (0.00%)  1/82 (1.22%) 
Ear and labyrinth disorders     
Cerumen impaction  0/80 (0.00%)  1/82 (1.22%) 
Eye disorders     
Lacrimation increased  0/80 (0.00%)  1/82 (1.22%) 
Gastrointestinal disorders     
Constipation  2/80 (2.50%)  3/82 (3.66%) 
Diarrhoea  2/80 (2.50%)  1/82 (1.22%) 
Nausea  6/80 (7.50%)  3/82 (3.66%) 
Vomiting  1/80 (1.25%)  2/82 (2.44%) 
Abdominal pain upper  1/80 (1.25%)  0/82 (0.00%) 
Tooth disorder  1/80 (1.25%)  0/82 (0.00%) 
Toothache  1/80 (1.25%)  0/82 (0.00%) 
General disorders     
Injection site pain  1/80 (1.25%)  2/82 (2.44%) 
Edema peripheral  2/80 (2.50%)  6/82 (7.32%) 
Catheter site erythema  1/80 (1.25%)  0/82 (0.00%) 
Feeling hot  1/80 (1.25%)  1/82 (1.22%) 
Injection site haematoma  1/80 (1.25%)  0/82 (0.00%) 
Tenderness  1/80 (1.25%)  0/82 (0.00%) 
Chills  0/80 (0.00%)  1/82 (1.22%) 
Device leakage  0/80 (0.00%)  1/82 (1.22%) 
Fatigue  0/80 (0.00%)  1/82 (1.22%) 
Feeling cold  0/80 (0.00%)  1/82 (1.22%) 
Injection site haemorrhage  0/80 (0.00%)  1/82 (1.22%) 
Medical device complication  0/80 (0.00%)  1/82 (1.22%) 
Thrombosis in device  0/80 (0.00%)  1/82 (1.22%) 
Infections and infestations     
Nasopharyngitis  3/80 (3.75%)  2/82 (2.44%) 
Urinary tract infection  3/80 (3.75%)  5/82 (6.10%) 
Sinusitis  1/80 (1.25%)  0/82 (0.00%) 
Staphylococcal abscess  1/80 (1.25%)  0/82 (0.00%) 
Urethritis  0/80 (0.00%)  1/82 (1.22%) 
Injury, poisoning and procedural complications     
Burn first degree  1/80 (1.25%)  0/82 (0.00%) 
Humerus fracture  1/80 (1.25%)  0/82 (0.00%) 
Procedural hypotension  1/80 (1.25%)  0/82 (0.00%) 
Vascular graft thrombosis  1/80 (1.25%)  0/82 (0.00%) 
Arthropod bite  0/80 (0.00%)  1/82 (1.22%) 
Fall  0/80 (0.00%)  1/82 (1.22%) 
Procedural hypertension  0/80 (0.00%)  1/82 (1.22%) 
Scratch  0/80 (0.00%)  1/82 (1.22%) 
Sunburn  0/80 (0.00%)  1/82 (1.22%) 
Investigations     
Blood glucose increased  1/80 (1.25%)  0/82 (0.00%) 
Breath sounds abnormal  1/80 (1.25%)  0/82 (0.00%) 
Weight increased  1/80 (1.25%)  0/82 (0.00%) 
Blood pressure increased  0/80 (0.00%)  1/82 (1.22%) 
Cardiac murmur  0/80 (0.00%)  1/82 (1.22%) 
Hepatic enzyme increased  0/80 (0.00%)  1/82 (1.22%) 
Metabolism and nutrition disorders     
Hyperkalaemia  3/80 (3.75%)  0/82 (0.00%) 
Hypoglycaemia  2/80 (2.50%)  3/82 (3.66%) 
Gout  1/80 (1.25%)  3/82 (3.66%) 
Hyperglycaemia  1/80 (1.25%)  1/82 (1.22%) 
Hyperkalaemia  0/80 (0.00%)  1/82 (1.22%) 
Vitamin D deficiency  0/80 (0.00%)  1/82 (1.22%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  4/80 (5.00%)  6/82 (7.32%) 
Myalgia  0/80 (0.00%)  2/82 (2.44%) 
Pain in extremity  1/80 (1.25%)  2/82 (2.44%) 
Flank pain  1/80 (1.25%)  1/82 (1.22%) 
Back pain  0/80 (0.00%)  1/82 (1.22%) 
Bone pain  0/80 (0.00%)  1/82 (1.22%) 
Limb discomfort  0/80 (0.00%)  1/82 (1.22%) 
Neck pain  0/80 (0.00%)  1/82 (1.22%) 
Synovial cyst  0/80 (0.00%)  1/82 (1.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Seborrhoeic keratosis  0/80 (0.00%)  1/82 (1.22%) 
Nervous system disorders     
Headache  3/80 (3.75%)  2/82 (2.44%) 
Parosmia  0/80 (0.00%)  4/82 (4.88%) 
Dizziness  1/80 (1.25%)  2/82 (2.44%) 
Dysgeusia  1/80 (1.25%)  1/82 (1.22%) 
Facial palsy  1/80 (1.25%)  1/82 (1.22%) 
Paraesthesia  1/80 (1.25%)  1/82 (1.22%) 
Unresponsive to stimuli  0/80 (0.00%)  1/82 (1.22%) 
Renal and urinary disorders     
Haematuria  1/80 (1.25%)  0/82 (0.00%) 
Nocturia  0/80 (0.00%)  1/82 (1.22%) 
Respiratory, thoracic and mediastinal disorders     
Cough  3/80 (3.75%)  0/82 (0.00%) 
Asthma  1/80 (1.25%)  0/82 (0.00%) 
Oropharyngeal pain  1/80 (1.25%)  0/82 (0.00%) 
Dyspnoea  0/80 (0.00%)  1/82 (1.22%) 
Epistaxis  0/80 (0.00%)  1/82 (1.22%) 
Rales  0/80 (0.00%)  1/82 (1.22%) 
Wheezing  0/80 (0.00%)  1/82 (1.22%) 
Skin and subcutaneous tissue disorders     
Ingrowing nail  1/80 (1.25%)  1/82 (1.22%) 
Acne  0/80 (0.00%)  1/82 (1.22%) 
Cold sweat  0/80 (0.00%)  1/82 (1.22%) 
Dry skin  0/80 (0.00%)  1/82 (1.22%) 
Ecchymosis  0/80 (0.00%)  1/82 (1.22%) 
Skin haemorrhage  0/80 (0.00%)  1/82 (1.22%) 
Social circumstances     
Treatment noncompliance  0/80 (0.00%)  1/82 (1.22%) 
Vascular disorders     
Hypotension  2/80 (2.50%)  8/82 (9.76%) 
Flushing  1/80 (1.25%)  0/82 (0.00%) 
Hot flush  1/80 (1.25%)  0/82 (0.00%) 
Hypertension  1/80 (1.25%)  1/82 (1.22%) 
Poor veneous access  0/80 (0.00%)  1/82 (1.22%) 
1
Term from vocabulary, MedDRA 13.0
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.
If there is no multi-site publication within 18 months after the Study has been completed or terminated at all Study sites, and all data has been received by Sponsor, the Site and SMO shall have the right to publish its results from the Study for non-commercial purposes, if submitted to Sponsor for review 60 days prior to submission of publication. Publication must remove all confidential information and may be delayed by up to 180 days to allow Sponsor to protect its interests.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: AMAG Pharmaceuticals, Inc.
Phone: 1-877-411-2510
EMail: amag@druginfo.com
Layout table for additonal information
Responsible Party: AMAG Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01052779    
Other Study ID Numbers: FER-CKD-201
2009-015630-30 ( EudraCT Number )
First Submitted: January 15, 2010
First Posted: January 20, 2010
Results First Submitted: March 26, 2018
Results First Posted: May 15, 2018
Last Update Posted: May 15, 2018