Trial Outcomes & Findings for A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease (NCT NCT00830037)

Last Updated: 2016-07-21

Results Overview

Plasma clearance of iothalamate was measured by administering an IV bolus of 5 mL of iothalamate meglumine and sampling 2 mL of blood at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 min after injection. Iothalamate was measured by high-performance liquid chromatography. Plasma clearance was calculated using a two-pool model using validated pharmacokinetic software. The mean modeled iothalamate mGFR slope (e.g., change from baseline to 2 years) in each group (IV iron vs. oral iron) was then calculated after adjustment for baseline log urinary protein/creatinine ratio.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

136 participants

Primary outcome timeframe

Baseline, 2 years

Results posted on

2016-07-21

Participant Flow

Participant milestones

Participant milestones
Measure	IV Iron IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.
Overall Study STARTED	67	69
Overall Study COMPLETED	49	50
Overall Study NOT COMPLETED	18	19

Reasons for withdrawal

Reasons for withdrawal
Measure	IV Iron IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.
Overall Study Withdrawal by Subject	2	3
Overall Study Lost to Follow-up	1	2
Overall Study Active when terminated by DSMB	15	14

Baseline Characteristics

A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV Iron n=67 Participants IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron n=69 Participants Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.	Total n=136 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 10.7 • n=5 Participants	67.8 years STANDARD_DEVIATION 11.5 • n=7 Participants	65.5 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	54 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized Black	27 participants n=5 Participants	18 participants n=7 Participants	45 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	38 participants n=5 Participants	51 participants n=7 Participants	89 participants n=5 Participants
eGFR	34.3 ml/min per 1.73m2 STANDARD_DEVIATION 10.2 • n=5 Participants	34.7 ml/min per 1.73m2 STANDARD_DEVIATION 10.0 • n=7 Participants	34.5 ml/min per 1.73m2 STANDARD_DEVIATION 10.0 • n=5 Participants
Proteinuria High proteinuria stratum (≥3g/g)	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Proteinuria Low proteinuria stratum (<3g/g)	58 participants n=5 Participants	60 participants n=7 Participants	118 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 2 years

Population: Modeled iothalamate mGFR slope (e.g., change from baseline to 2 years) was calculated for each group (IV iron vs. oral iron) after adjustment for baseline log urinary protein/creatinine ratio.

Outcome measures

Outcome measures
Measure	IV Iron n=67 Participants IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron n=69 Participants Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.
Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron	-4.0 Slope (ml/min per 1.73m2 per year)	-3.6 Slope (ml/min per 1.73m2 per year)

SECONDARY outcome

Timeframe: Baseline, 2 years

Proteinuria was estimated using measurements of urinary protein and creatinine before iron administration at baseline and at periodic intervals thereafter. Mean change from baseline log urinary protein/creatinine ratio (g/g) is reported at 2 years.

Outcome measures

Outcome measures
Measure	IV Iron n=67 Participants IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron n=69 Participants Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.
Proteinuria	0.287 g/g Interval 0.053 to 0.521	0.251 g/g Interval 0.019 to 0.484

Adverse Events

IV Iron

Serious events: 37 serious events

Other events: 45 other events

Deaths: 0 deaths

Oral Iron

Serious events: 40 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Rajiv Agarwal, MD, FAHA, FASN, FASH

Indiana University School of Medicine & Richard L Roudebush VA Medical Center

Phone: 317-988-2241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	IV Iron n=67 participants at risk IV Iron: IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.	Oral Iron n=69 participants at risk Ferrous Sulfate: Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.
Infections and infestations Skin infection	10.4% 7/67 • Number of events 11 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	8.7% 6/69 • Number of events 6 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Infections and infestations Bone infection	4.5% 3/67 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	2.9% 2/69 • Number of events 7 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Infections and infestations Lung infection	11.9% 8/67 • Number of events 11 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	5.8% 4/69 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Infections and infestations Urinary tract infection	4.5% 3/67 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	4.3% 3/69 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Infections and infestations Sepsis	7.5% 5/67 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Infections and infestations Infections and infestations - other, miscellaneous	1.5% 1/67 • Number of events 1 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	2.9% 2/69 • Number of events 3 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Heart failure	13.4% 9/67 • Number of events 28 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	13.0% 9/69 • Number of events 15 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Chest pain - cardiac	3.0% 2/67 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	2.9% 2/69 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Myocardial infarction	11.9% 8/67 • Number of events 9 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	11.6% 8/69 • Number of events 9 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Nervous system disorders Stroke	3.0% 2/67 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	0.00% 0/69 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Ventricular arrhythmia	6.0% 4/67 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	5.8% 4/69 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Pulmonary valve disease	3.0% 2/67 • Number of events 3 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Cardiac disorders Cardiac disorders - other, miscellaneous	7.5% 5/67 • Number of events 6 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	5.8% 4/69 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Renal and urinary disorders Acute kidney injury	17.9% 12/67 • Number of events 21 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	21.7% 15/69 • Number of events 22 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Metabolism and nutrition disorders Hyperkalemia	3.0% 2/67 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	7.2% 5/69 • Number of events 6 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Renal and urinary disorders Renal and urinary disorders - other, miscellaneous	4.5% 3/67 • Number of events 3 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 1 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, cancer-related	6.0% 4/67 • Number of events 8 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	5.8% 4/69 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Surgical and medical procedures Surgical and medical procedures - other, PRBC transfusion	17.9% 12/67 • Number of events 19 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	17.4% 12/69 • Number of events 17 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Gastrointestinal disorders Gastrointestinal disorders - other, GI bleed	0.00% 0/67 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	7.2% 5/69 • Number of events 7 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Metabolism and nutrition disorders Hyperglycemia	3.0% 2/67 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 1 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/67 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	4.3% 3/69 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Eye disorders Retinopathy	1.5% 1/67 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 2 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Vascular disorders Hypertension	4.5% 3/67 • Number of events 5 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	1.4% 1/69 • Number of events 1 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Renal and urinary disorders Urinary retention	3.0% 2/67 • Number of events 3 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	2.9% 2/69 • Number of events 3 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
General disorders General disorders and administration site conditions - other, miscellanous	29.9% 20/67 • Number of events 27 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	30.4% 21/69 • Number of events 33 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
Renal and urinary disorders Renal and urinary disorders - other, end stage renal disease	9.0% 6/67 • Number of events 6 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	10.1% 7/69 • Number of events 7 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.
General disorders Death NOS	9.0% 6/67 • Number of events 6 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.	5.8% 4/69 • Number of events 4 • Adverse event data were routinely collected at 2, 4, 6, and 8 weeks after randomization during the treatment phase and again at 3, 6, 12, 18, and 24 months after randomization during the follow-up phase.