Clinical trial • Phase IV • Cardiology

ferric carboxymaltose for Chronic heart failure | Iron deficiency

Phase IV trial of ferric carboxymaltose for Chronic heart failure | Iron deficiency.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Chronic heart failure | Iron deficiency
Trial Stage
Phase IV
Drug Modality
Small molecule|Other

Key dates

Initial CTIS Submission Date
26-11-2024
First CTIS Authorization Date
21-01-2025

Trial design

Randomised, open-label, control group: ferric carboxymaltose (ferinject®) — dose between 500 and 2000 mg (depending on weight and hb values), to be administered in 1 or 2 doses (time 0 ± 6 weeks) with possible further administration of 500 mg at week 12 if persistent iron deficiency. sucrosomial iron group: sucrosomial iron (sideral forte®) 60 mg (2 tablets) once daily for 24 weeks. sucrosomial iron + vitamin d group: sucrosomial iron (sideral forte®) 60 mg (2 tablets) once daily + vitamin d3 (100000 iu loading dose with dibase® at time 0, then 2,000 iu daily with ultrad3®) for 24 weeks. Phase IV trial across 1 site in Italy.

Randomised
Yes
Open Label
Yes
Comparator
Control group: Ferric carboxymaltose (Ferinject®) — dose between 500 and 2000 mg (depending on weight and Hb values), to be administered in 1 or 2 doses (time 0 ± 6 weeks) with possible further administration of 500 mg at week 12 if persistent iron deficiency. Sucrosomial iron group: Sucrosomial iron (SiderAl Forte®) 60 mg (2 tablets) once daily for 24 weeks. Sucrosomial iron + vitamin D group: Sucrosomial iron (SiderAl Forte®) 60 mg (2 tablets) once daily + Vitamin D3 (100000 IU loading dose with Dibase® at time 0, then 2,000 IU daily with UltraD3®) for 24 weeks.
Target Sample Size
258
Trial Duration For Participant
168

Stratification factors

  • gender
  • age

Eligibility

Recruits 258 Vulnerable population not selected; participants must be at least 18 years of age. A subject information and informed consent form is available (ICF_vers 1_5_11_11_24). No assent or minor-consent procedures are described..

Pregnancy Exclusion
pregnancy or breastfeeding;
Vulnerable Population
Vulnerable population not selected; participants must be at least 18 years of age. A subject information and informed consent form is available (ICF_vers 1_5_11_11_24). No assent or minor-consent procedures are described.

Inclusion criteria

  • {"criterion_text":"- Stable symptomatic chronic heart failure (NYHA functional class II-III) and all of the following:\n- at least 3 weeks since the last hospitalization or emergency department access for acute HF\n- optimal drug treatment for heart failure (HF) according to the ESC guidelines determined by the investigator (unless contraindications or treatment not tolerated)\n- no changes in HF therapy dose in the previous 2 weeks (except diuretics)\n- no new HF therapy in the 3 weeks prior to recruitment\n- left ventricle ejection fraction <=45%\n- brain natriuretic peptide >100 pg/mL and/or N-terminal-pro-brain natriuretic peptide >400 pg/mL at pre-recruitment evaluation\n- evidence of iron deficiency defined as ferritin <100 ng/ml or TSAT <20% in the case of ferritin levels between 100 and 300 ng/ml\n- vitamin D levels <50 nmol/L\n- the subject must be able to complete the 6-Minute-Walking -Test\n- at least 18 years of age."}

Exclusion criteria

  • {"criterion_text":"- Myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke, coronary artery bypass, percutaneous intervention, or major thoracic or cardiac surgery within the previous 2 months\n- clinically relevant (severe) non-corrected valvular heart disease, obstructive cardiomyopathy\n- chronic anemia due to non-correctable causes other than iron deficiency and anemia of chronic disease (e.g., hemoglobinopathies, hematologic malignancies, hemolytic anemia)\n- anemia due to vitamin B12 or acid folic deficiency (recruitment may be re-evaluated at least 6 weeks after the end of vitamin B12 and or folic acid supplementation)\n- history of acquired iron overload\n- administration of erythropoietin, iron supplementation (either oral or intravenous iron), blood transfusion in the previous 6 weeks or already scheduled for 3 months after recruitment\n- administration of vitamin D or similar in the 3 months preceding or already scheduled for the 3 months following recruitment\n- severe bone disease\n- active infections (C-reactive protein >20 mg/L)\n- clinically significant bleeding\n- active neoplasm (with exception of basal cell or squamous cell carcinoma of the skin and intraepithelial cervical neoplasia)\n- chronic liver disease (including active hepatitis) and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x normal limit\n- immunosuppressive therapy or dialysis\n- pregnancy or breastfeeding;\n- the subject has a known sensitivity to any of the products that will be administered during the study protocol."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The performance of the Six-Minute Walking Test (6MWT), comparing the mean difference from baseline of the distance walked by patients in meters.","definition_or_measurement_approach":"Comparison of mean difference from baseline in distance walked (meters) at 6MWT."}

Secondary endpoints

  • {"endpoint_text":"- Assess in the tree-arms treatment during the study the change in Kansas City Cardiomyopathy Questionnaire(KCCQ) score, NYHA class, echocardiographic parameters (parameters of systolic and diastolic function, parietal thicknesses, and left ventricular diameters), calcium and phosphorus profile (levels of calcium, phosphate and human Fibroblast Growth Factors), incidence of fractures, glomerular filtration rate, surviving days out of hospital, hospitalizations and mortality","definition_or_measurement_approach":"Change from baseline in KCCQ score; change in NYHA class; changes in echocardiographic systolic/diastolic parameters and dimensions; measurement of calcium/phosphate and FGF levels; incidence counts for fractures, hospitalizations, surviving days out of hospital and mortality during follow-up."}

Recruitment

Planned Sample Size
258
Recruitment Window Months
32
Consent Approach
Informed consent obtained from adult participants (≥18). Subject information and informed consent form is available (ICF_vers 1_5_11_11_24). No assent or paediatric consent procedures described. Languages of consent not specified.

Methods

  • Sequential recruitment of outpatients diagnosed with symptomatic chronic heart failure (NYHA II-III) and iron deficiency.
  • Pre-randomization of inpatients hospitalized for acute HF episodes with re-evaluation for recruitment during an outpatient visit scheduled at least 3 weeks after stabilization.

Geography

Total Number Of Sites
1
Total Number Of Participants
258

Italy

Earliest CTIS Part Ii Submission Date
10-12-2024
Latest Decision Or Authorization Date
21-01-2025
Processing Time Days
42
Number Of Sites
1
Number Of Participants
258

Sites

Site Name
Azienda Ospedaliera di Padova
Department Name
DIMED
Principal Investigator Name
Federico Capone
Principal Investigator Email
federico.capone@unipd.it
Contact Person Name
Federico Capone
Contact Person Email
federico.capone@unipd.it

Sponsor

Primary sponsor

Full Name
Universita Degli Studi Di Padova
Organisation Type
Educational Institution
Country Of Registered Address
Italy

Third parties

  • {"country":"","full_name":"PharmaNutra Spa","duties_or_roles":"Source of monetary support","organisation_type":""}

Investigational products

Investigational Product Name
Ferinject (ferric carboxymaltose)
Active Substance
ferric carboxymaltose
Modality
Other
Routes Of Administration
Intravenous injection/infusion
Route
Intravenous
Authorisation Status
Authorised (AIC 040251035)
Starting Dose
500 mg (lower range of planned dose)
Dose Levels
500-2000 mg depending on weight and Hb; possible further 500 mg at week 12 if persistent iron deficiency
Frequency
1 or 2 doses at time 0 ±6 weeks; possible additional 500 mg at week 12
Maximum Dose
2000 mg (with possible additional 500 mg at week 12; product maxTotalDose indicated as 2500 mg)
Dose Escalation Increase
Initial 500-2000 mg; possible additional 500 mg at week 12
Investigational Product Name
Sucrosomial iron (SiderAl Forte®)
Modality
Other
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Registered as nutritional supplement (Registro degli Integratori) / EAN listed
Starting Dose
60 mg (2 tablets) once daily
Dose Levels
60 mg once daily for 24 weeks
Frequency
Once daily
Maximum Dose
60 mg daily
Investigational Product Name
Vitamin D3 (Dibase® 100000 U.I. then UltraD3® maintenance)
Active Substance
colecalciferol
Modality
Small molecule
Routes Of Administration
Intramuscular/injection (loading) and oral (maintenance)
Route
Loading: injection; Maintenance: oral
Authorisation Status
Authorised (AIC 036635023 for Dibase® injection)
Starting Dose
100000 IU loading dose at time 0 (Dibase®), then 2,000 IU daily (UltraD3®)
Dose Levels
100000 IU once (loading) then 2000 IU daily for 24 weeks
Frequency
Loading once at time 0; then daily maintenance (2000 IU)
Maximum Dose
100000 IU single loading dose; 2000 IU daily maintenance
Investigational Product Name
UltraD3® (maintenance vitamin D3 preparation)
Active Substance
colecalciferol
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Registered (vitamin supplement listing/EAN)
Starting Dose
2000 IU daily
Dose Levels
2000 IU daily for 24 weeks
Frequency
Once daily
Maximum Dose
2000 IU daily
Combination Treatment
Yes

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