Effects of intravenous iron therapy with ferric carboxymaltose compared with oral irontherapy in heart failure with preserved ejection fraction and iron deficiency. ( PREFER-HF)

Phase 1

• Conditions: Patients with heart failure with preserved ejection fraction ( HFpEF) and iron deficency anemia.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-003604-31-ES
• Lead Sponsor: José Luis Morales Rull, Institut de Recerca Biomédica Lleida IRB Hospital Arnau de Vilanova Servicio de Medicina Interna

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-17
• Last Update Posted: 13 February 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal
pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
2. Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization).
3. BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.
4. Subject must be capable of completing the 6MWT.
5. Screening serum ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%.
6. At least 18 years of age.
7. Before any study-specific procedure, the appropriate written informed consent must be obtained.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
;
1. Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal
pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
2. Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization).
3. BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.
4. Subject must be capable of completing the 6MWT.
5. Screening serum ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%.
6. At least 18 years of age.
7. Before any study-specific procedure, the appropriate written informed consent must be obtained.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
;
1. Subjects with stable chronic HF (NYHA II/IV functional class) on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). In general, optimal
pharmacological treatment should include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a beta blocker unless contraindicated or not tolerated and diuretic if indicated.
2. Left ventricular ejection fraction >45% (value within 3 months of planned date of randomization).
3. BNP >100 pg/mL and/or N-terminal-pro-BNP >400 pg/mL at the screening visit.
4. Subject must be capable of completing the 6MWT.
5. Screening serum ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%.
6. At least 18 years of age.
7. Before any study-specific procedure, the appropriate written informed consent must be obtained.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. Subject has known sensitivity to any of the products to be administered during dosing.
2. History of acquired iron overload.
3. History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior to randomization.
4. Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing
iron <75 mg/day is permitted.
5. Body weight =/<35 kg.
6. Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
7. Subject at an immediate need of transfusion or haemoglobin >/= 15 g/dL.
8. Known active bacterial infection.
9. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
10. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
11. Vitamin B12 and/or serum folate deficiency. If deficiency-corrected subject may be rescreened for inclusion.
12. Subjects with known seropositivity to human immunodeficiency virus.
13. Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
14. Currently receiving systemic chemotherapy and/or radiotherapy.
15. Renal dialysis (previous, current, or planned within the next 6 months).
16. Unstable angina pectoris as judged by the investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute.
17. Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack, or stroke within the last 3 months prior to randomization.
18. Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.
19. Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
20. Subject of childbearing potential who is pregnant (e.g. positive human chorionic gonadotropin test) or is breastfeeding.
21. Subject is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
22. Subject previously randomized to this study. Note: subjects may be rescreened if they fail any of the screening procedures. If rescreened, all tests must fall inside the maximum specified screening windows for each criterion.
23. Subject will not be available for all protocol-specified assessments.
24. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
25. Lactose intolerance.
26. Pregnant woman.
;
1. Subject has known sensitivity to any of the products to be administered during dosing.
2. History of acquired iron overload.
3. History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior to randomization.
4. Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing
iron <75 mg/day is permitted.
5. Body weight =/<35 kg.
6. Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
7. Subject at an immediate need of transfusion or haemoglobin >/= 15 g/dL.
8. Known active bacterial infection.
9. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
10. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
11. Vitamin B12 and/or serum folate deficiency. If deficiency-corrected subject may be rescreened for inclusion.
12. Subjects with known seropositivity to human immunodeficiency virus.
13. Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
14. Currently receiving systemic chemotherapy and/or radiotherapy.
15. Renal dialysis (previous, current, or planned within the next 6 months).
16. Unstable angina pectoris as judged by the investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute.
17. Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack, or stroke within the last 3 months prior to randomization.
18. Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.
19. Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
20. Subject of childbearing potential who is pregnant (e.g. positive human chorionic gonadotropin test) or is breastfeeding.
21. Subject is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
22. Subject previously randomized to this study. Note: subjects may be rescreened if they fail any of the screening procedures. If rescreened, all tests must fall inside the maximum specified screening windows for each criterion.
23. Subject will not be available for all protocol-specified assessments.
24. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
25. Lactose intolerance.
26. Pregnant woman.
;
1. Subject has known sensitivity to any of the products to be administered during dosing.
2. History of acquired iron overload.
3. History of erythropoietin-stimulating agent, i.v. iron therapy, and/or blood transfusion in previous 6 weeks prior to randomization.
4. Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization. Note: ongoing use of multivitamins containing
iron <75 mg/day is permitted.
5. Body weight =/<35 kg.
6. Exercise training programme(s) in the 3 months prior to screening or planned in the next 6 months.
7. Subject at an immediate need of transfusion or haemoglobin >/= 15 g/dL.
8. Known active bacterial infection.
9. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
10. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
11. Vitamin B12 and/or serum folate deficiency. If deficiency-corrected subject may be rescreened for inclusion.
12. Subjects with known seropositivity to human immunodeficiency virus.
13. Clinical evidence of current malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia.
14. Currently receiving systemic chemotherapy and/or radiotherapy.
15. Renal dialysis (previous, current, or planned within the next 6 months).
16. Unstable angina pectoris as judged by the investigator; severe valvular or left ventricular outflow obstruction disease needing intervention; atrial fibrillation/flutter with a mean ventricular response rate at rest >100 beats per minute.
17. Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack, or stroke within the last 3 months prior to randomization.
18. Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.
19. Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
20. Subject of childbearing potential who is pregnant (e.g. positive human chorionic gonadotropin test) or is breastfeeding.
21. Subject is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
22. Subject previously randomized to this study. Note: subjects may be rescreened if they fail any of the screening procedures. If rescreened, all tests must fall inside the maximum specified screening windows for each criterion.
23. Subject will not be available for all protocol-specified assessments.
24. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
25. Lactose intolerance.
26. Pregnant woman.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified