Clinical trial NCT00994318: Ferric Carboxymaltose (FCM) Assessment in Subjects With Iron Deficiency Anaemia and Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
Official title: An Open-label, Multicentre, Randomised, 3-arm Study to Investigate the Comparative Efficacy and Safety of Intravenous Ferric Carboxymaltose (Ferinject High and Low Dosage Regimens) Versus Oral Iron for the Treatment of Iron Deficiency Anaemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Iron Deficiency Anaemia
Chronic Kidney Disease
Keywords: Ferinject Iron Deficiency Anaemia Chronic Kidney Disease
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
Collaborators: name: American Regent, Inc.
name: ICON Clinical Research
First posted: 2009-10-14
Enrollment: 626
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase IIIb study to evaluate the long-term efficacy of ferric carboxymaltose (FCM) (using targeted ferritin levels to determine dosing) or oral iron in non-dialysis-dependent chronic kidney disease (NDD-CKD) subjects with iron deficiency anaemia (IDA).

Detailed description: After an initial screening period of up to 4 weeks, eligible subjects were randomised (1:1:2) to 1 of the following 3 treatment arms for a period of 52 weeks.

1. FCM regimen (maximum single intravenous doses of 1,000 mg of iron) targeting a ferritin level of 400-600 mcg/L.
2. FCM regimen (maximum single intravenous doses of 200 mg of iron) targeting a ferritin level of 100-200 mcg/L.
3. Daily oral iron with 200 mg iron/day (100 mg twice daily)

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age.
2. NDD-CKD subjects with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 using modification of diet in renal disease 4 (MDRD-4) calculation.
3. NDD-CKD subjects with an eGFR loss ≤12 mL/min/1.73 m2/year and a predicted eGFR of ≥15 mL/min/1.73 m2 in 12 months.
4. Any single Hb between 9 and 11 g/dL within 4 weeks of randomisation. A value taken as part of routine medical care was used.
5. Any single serum ferritin \<100 mcg/L or \<200 mcg/L with TSAT \<20% within 4 weeks of randomisation. Measurements taken as part of routine medical care were used.
6. ESA naïve; no exposure to ESA in last 4 months prior to randomisation.
7. Females of childbearing potential must have had a negative pregnancy test, using any medically acceptable assessment, prior to randomisation.
8. Before any study specific procedure, the appropriate written informed consent must have been obtained.

Exclusion Criteria:

1. History of acquired iron overload.
2. Known hypersensitivity reaction to any component of ferrous sulphate or FCM. Subjects with hypersensitivity to other forms of iron were permitted to participate.
3. Documented history of discontinuing oral iron products due to significant gastrointestinal (GI) distress.
4. Screening TSAT \>40%.
5. Known active infection, C-reactive protein \>20 mg/L, clinically significant overt bleeding, active malignancy (i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia).
6. History of chronic alcohol abuse (alcohol consumption \>40 g/day).
7. Chronic liver disease and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.
8. Active human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome or active hepatitis B or C virus infection.
9. Anaemia due to reasons other than iron deficiency (e.g., haemoglobinopathy). Subjects with treated Vitamin B12 or folic acid deficiency were permitted.
10. IV iron and/or blood transfusion in previous 30 days prior to screening (or during the screening period).
11. Oral iron therapy at doses \>100 mg/day dosing must have been discontinued at least 1 week prior to randomisation. If subject had received this therapy for \>3 months (at doses \>100 mg/day) then subject was not eligible. Ongoing use of multivitamins containing iron was permitted.
12. Immunosuppressive therapy that may have led to anaemia (e.g., cyclophosphamide, azathioprine, or mycophenolate mofetil). Steroid therapy was permitted.
13. Currently requiring renal dialysis.
14. Anticipated dialysis or transplant during the study.
15. Anticipated need for surgery that may have resulted in significant bleeding (\>100 mL).
16. Currently suffering from chronic heart failure New York Heart Association Class IV.
17. Poorly controlled hypertension (\>160 mmHg systolic pressure or \>100 mmHg diastolic pressure).
18. Acute coronary syndrome or stroke within the 3 months prior to screening.
19. Currently suffering from concomitant, severe psychiatric disorders or other conditions which, in the opinion of the Investigator, would have made participation unacceptable.
20. Subject was not using adequate contraceptive precautions.
21. Subject of childbearing potential was evidently pregnant (e.g., positive human chorionic gonadotropin test) or was breast feeding.
22. Body weight \<35 kg.
23. Subject currently was enrolled in or had not yet completed at least 30 days since ending other investigational device or drug studies, or subject was receiving other investigational agent(s).
24. Subject would not be available for follow-up assessment.
25. Subject had any kind of disorder that compromised the ability of the subject to give written informed consent and/or to comply with study procedures.

Primary outcomes:
measure: Kaplan-Meier Survival Analysis for Time to Other Anemia Therapy or Hb Trigger
timeFrame: Up to 1 year after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Gosford
country: Australia
facility: Gosford Hospital - Renal Research
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin IV
city: Baudour
country: Belgium
facility: RHMS Baudour - Department of Nephrology and Dialysis
city: Novy Jicin
country: Czech Republic
facility: Nemocnice s poliklinikou v Novem Jicine, p.o. p.o. Interni oddeleni - nefrologie a dialyza
city: Frederica
country: Denmark
facility: Lillebalt Frederica Sygehus Department of Nephrology
city: Grenoble Cedex
country: France
facility: CHU grenoble - Service de Nephrologie
city: Demmin
country: Germany
facility: Praxis Dr. Kraatz
city: Arta
country: Greece
facility: General Hospital of Arta - Nephrology Department
city: Anzio
country: Italy
facility: Ospedali Riuniti Anzio-Nettuno ASL ROMA H U.O. Nefrologia e Dialisi
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum - Locatie Amersfoort Lichtenberg
city: Trondheim
country: Norway
facility: St. Olav's Hospital
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Spec. Oddzial I Wewnetrzny I Nefrologii
city: Lisboa
country: Portugal
facility: Hospital Santa Maria - Nefrologia
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Nefrologie"Dr Carol Davila"
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla - Servicio de Nefrología
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty Balcali Hospital - Department of Nephrology
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: King's College Hospital NHS Trust
name: Iain Macdougall
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roger SD, Gaillard CA, Bock AH, Carrera F, Eckardt KU, Van Wyck DB, Cronin M, Meier Y, Larroque S, Macdougall IC; FIND-CKD Study Investigators. Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant. 2017 Sep 1;32(9):1530-1539. doi: 10.1093/ndt/gfw264.
citation: Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Meier Y, Larroque S, Roger SD; FIND-CKD Study investigators. Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial. BMC Nephrol. 2017 Jan 17;18(1):24. doi: 10.1186/s12882-017-0444-6.
citation: Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Roubert B, Nolen JG, Roger SD; FIND-CKD Study Investigators. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014 Nov;29(11):2075-84. doi: 10.1093/ndt/gfu201. Epub 2014 Jun 2.