Iron deficiency anaemia Haematological Disorders Iron deficiency anaemia
Conditions
Interventions
VIT-45 (ferric carboxymaltose) injections and Venofer® (Iron sucrose) injections:
Ferric carboxymaltose:
Aqueous solution containing 50 mg/mL iron administered by dilu
Sponsors
Vifor Pharma (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult, male or female, between the ages of 18 and 80 years (inclusive) requiring haemodialysis/haemodiafiltration with iron deficiency secondary to chronic renal failure 2. IDA defined as haemoglobin (Hb) less than or equal to 115 g/L and at least one of the following: 2.1. Transferrin saturation (TfS) less than 20% 2.2. Serum ferritin less than 200 µg/L Initially, a total of 120 patients (60 in each treatment group) were enrolled with a Hb value of less than or equal to 100 g/L. Following amendment 2, this was adjusted such that in each treatment group at least 50% of patients (at least 60 in each treatment group) were enrolled with a Hb value of less than or equal to 100 g/L 3. Patients treated with EPO (including epoetin alfa, epoetin beta, and darbepoetin alfa) must have received this treatment for at least 8 weeks prior to inclusion in the study. The EPO dose may have been decreased during the study at the discretion of the investigator; increases in the dose of EPO were not permitted. 4. Permanent vascular access appropriate for haemodialysis/haemodiafiltration 5. Females of childbearing potential must have had a negative serum pregnancy test at screening and agreed to practise an acceptable method of birth control during the study and for up to one month after the last dose of the study medication. Acceptable methods of birth control included barrier methods (including male and female condoms), diaphragms (cervical caps) with intravaginal spermicide (including jellies, foams and suppositories), intra-uterine devices or hormonal contraceptives. Non-childbearing potential included being surgically sterilised at least 6 months prior to the study or post-menopausal with no menstrual bleeding for at least 2 years prior to the study. Fertile males agreed to ensure that they use adequate contraception during the study. 6. Demonstrated the ability to understand the requirements of the study, willingness to provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
Exclusion criteria
Exclusion criteria: 1. Body weight less than 40 kg 2. Blood transfusion or oral or parenteral iron treatment within 30 days prior to enrolment, or anticipated need for a blood transfusion during the study 3. Documented hypersensitivity to components of VIT-45 or Venofer® 4. Other types of anaemia (especially haemolytic, macrocytic, hypoplastic, or sideroblastic anaemia) 5. Haemochromatosis or other iron storage disorders. Addition of haemodiafiltration was introduced following protocol amendment 1. 6. Untreated vitamin B12 or folic acid deficiency (deficiency defined as below the normal range). Patients with subnormal vitamin B12 levels were included if all of the following criteria are met: 6.1. No suspicion of atrophic gastritis 6.2. No history of resection of large parts of the stomach or upper intestine 6.3. Treatment of vitamin B12 deficiency was started prior to randomisation 7. Treatment with an investigational drug within the 30 days prior to enrolment 8. History of addiction to drugs or chronic alcohol abuse 9. Prior use of VIT-45 or prior participation in other studies of VIT-45 10. Myelosuppressive therapy or need for surgery 11. Active severe infection or malignancy other than carcinoma in situ of the cervix and non-melanoma skin cancer 12. Active liver disease. Patients who were positive for hepatitis B surface-antigen (HbsAg) or hepatitis C virus antibody (anti-HCV) were excluded if they had abnormal liver function test (LFT) results 13. Significant cardiovascular disease, including myocardial infarction within 12 months prior to study inclusion, congestive heart failure (New York Heart Association grade III or IV), or poorly controlled hypertension according to the judgement of the investigator 14. Positive for human immunodeficiency virus-1 (HIV)-1/HIV-2 antibodies (anti-HIV) 15. Pregnant women or nursing mothers 16. Endocrinologic or metabolic disorders that were not controlled
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of patients reaching an increase in Hb of greater than or equal to 10 g/L at 4 weeks after baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum increase in Hb, ferritin and TfS during study participation 2. Change from baseline levels of Hb, serum ferritin, and TfS, at weeks 1, 2 and 4 and the follow-up visit 3. The number and proportion of patients who, at weeks 1, 2, and 4, and the follow-up visit, achieved target levels of: 3.1. Hb: greater than or equal to 110 g/L in patients with a baseline Hb greater than or equal to 100 g/L or less than or equal to 120 g/L in patients with a baseline Hb greater than 100 g/L to less than or equal to 115 g/L 3.2. Serum ferritin: 200 to 800 µg/L 3.3. TfS: 20 to 50% 4. The individual area under the plasma concentration time curve (AUC) of change from baseline levels of Hb, serum ferritin and TfS, standardised per day of study participation Safety: 5. Adverse events (AEs): type, nature, incidence and outcome 6. Vital signs (axillary temperature, blood pressure and heart rate) and weight (added by Amendment no 1) 7. 12-lead electrocardiogram (ECG) including documentation of QT and RR intervals 8. Physical examinations 9. Clinical laboratory panels (haematology/coagulation and clinical chemistry) 10. Discontinuation of treatment due to AEs | — |
Countries
Belgium, Bulgaria, Poland, Romania, Russian Federation, Slovakia, Ukraine
Outcome results
None listed