Ferric Carboxymaltose (FCM) Assessment in Subjects With Iron Deficiency Anaemia and Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)

NCT ID: NCT00994318

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 626 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2014-02-28

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)

Conditions

Chronic Kidney Disease; Iron Deficiency Anaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FCM (high ferritin target)

Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 400 - 600 mcg/L

Group Type: EXPERIMENTAL

FCM (Ferric carboxymaltose) high ferritin target

Intervention Type: DRUG

FCM (low ferritin target)

Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 100 - 200 mcg/L

Group Type: EXPERIMENTAL

FCM (Ferric carboxymaltose) low ferritin target

Intervention Type: DRUG

Oral Iron

Ferrous sulphate 100 mg iron twice daily, continuous

Group Type: ACTIVE_COMPARATOR

Oral Iron (Ferrous sulphate)

Intervention Type: DRUG

Interventions

FCM (Ferric carboxymaltose) high ferritin target

Intervention Type: DRUG

FCM (Ferric carboxymaltose) low ferritin target

Intervention Type: DRUG

Oral Iron (Ferrous sulphate)

Intervention Type: DRUG

Other Intervention Names

Ferinject; Injectafer; Ferinject; Injectafer; Ferrous sulphate

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Regent, Inc.

INDUSTRY

Sponsor Role: collaborator

ICON Clinical Research

INDUSTRY

Sponsor Role: collaborator

Vifor Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iain Macdougall

Role: PRINCIPAL_INVESTIGATOR

King's College Hospital NHS Trust

Locations

Trial Management Associates

Wilmington, North Carolina, United States

Gosford Hospital - Renal Research

Gosford, , Australia

Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin IV

Innsbruck, , Austria

RHMS Baudour - Department of Nephrology and Dialysis

Baudour, , Belgium

Nemocnice s poliklinikou v Novem Jicine, p.o. p.o. Interni oddeleni - nefrologie a dialyza

Nový Jičín, , Czechia

Lillebalt Frederica Sygehus Department of Nephrology

Frederica, , Denmark

CHU grenoble - Service de Nephrologie

Grenoble, , France

Praxis Dr. Kraatz

Demmin, , Germany

General Hospital of Arta - Nephrology Department

Arta, , Greece

Ospedali Riuniti Anzio-Nettuno ASL ROMA H U.O. Nefrologia e Dialisi

Anzio, , Italy

Meander Medisch Centrum - Locatie Amersfoort Lichtenberg

Amersfoort, , Netherlands

St. Olav's Hospital

Trondheim, , Norway

Miedzyleski Szpital Spec. Oddzial I Wewnetrzny I Nefrologii

Warsaw, , Poland

Hospital Santa Maria - Nefrologia

Lisbon, , Portugal

Spitalul Clinic de Nefrologie"Dr Carol Davila"

Bucharest, , Romania

Hospital Universitario Marqués de Valdecilla - Servicio de Nefrología

Santander, , Spain

Karolinska University Hospital

Stockholm, , Sweden

Cukurova University Medical Faculty Balcali Hospital - Department of Nephrology

Adana, , Turkey (Türkiye)

King's College Hospital

London, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Czechia; Denmark; France; Germany; Greece; Italy; Netherlands; Norway; Poland; Portugal; Romania; Spain; Sweden; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28339831 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28095881 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24891437 (View on PubMed)

Other Identifiers

FER-CKD-01

Identifier Type: -

Identifier Source: org_study_id