Chronic Heart Failure MedDRA version: 18.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Trade Name: MONOFER
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: ferric iron (FE 3+)
CAS Number: 9004-66-04
Other descriptive name: IRON(III) ISOMALTOSIDE 1000
Concentrati
Sponsors
King's College London
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: =30 years of age and have signed written informed consent • Stable symptomatic CHF; NYHA III/IV and LVEF =45%, or if NYHA II then LVEF must be =40% as assessed within last 6 months using echocardiographic or magnetic resonance imaging techniques. • On optimal conventional therapy for at least 4 weeks prior to recruitment and without dose changes for at least 2 weeks. • Screening Hb concentration =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • History of acquired iron overload, known haemochromatosis or first relatives with haemochromatosis, and allergic disorders (asthma, eczema, and anaphylactic reactions). • Known hypersensitivity to parental iron preparations or any of their excipients. • Known active infection, bleeding, malignancy, haemolytic anaemia, and rheumatoid arthritis. • History of chronic liver disease with alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the upper limit of the normal range, severe chronic lung disease with FEV1 110 bpm), uncontrolled symptomatic brady- or tachyarrhythmias. • Musculoskeletal limitation that, in the investigators judgement, would impair exercise testing. • Pregnant or breast-feeding • Inability to comprehend study protocol • Parallel participation in another clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of iv iron repletion on skeletal muscle oxidative capacity as quantified by PCr t1/2 and ADP t1/2 following gastrocnemius muscle exercise using 31-P MRS. ;Secondary Objective: To determine: • Change in skeletal muscle ferritin, free iron content, and transferrin receptor levels from baseline to 2 weeks post treatment. • Change in skeletal muscle fibre type, immunohistochemistry, and aerobic enzyme levels from baseline to 2 weeks post treatment. • Change in distance walked in 6 minutes from baseline to 2 weeks post treatment. • Change in symptom status from baseline to 2 weeks post treatment. • Change in haematological and biochemical indices from baseline to 2 weeks post treatment. • Number and incidence of adverse events; changes in liver function tests and renal function tests; changes in vital parameters.;Primary end point(s): Change in skeletal muscle oxidative capacity as assessed by PCr t1/2 from baseline to 2 weeks post last treatment.;Timepoint(s) of evaluation of this end point: Endpoint will be evaluated at baseline and study end (2 weeks post last treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in skeletal muscle oxidative capacity as assessed by ADP t1/2 from baseline to 2 weeks post last treatment. • Change in skeletal muscle oxidative capacity as reflected by mitochondrial oxygen consumption per mg of muscle tissue measured using a respirometer from baseline to 2 weeks post last treatment. • Change in skeletal muscle ferritin, free iron content, and transferrin receptor levels from baseline to 2 weeks post last treatment. • Change in skeletal muscle fibre type, immunohistochemistry, and aerobic enzyme mRNA and protein levels from baseline to 2 weeks post last treatment. • Change in distance walked in 6 minutes from baseline to 2 weeks post last treatment. • Change in cardiopulmonary exercise (CPEX) parameters (peak oxygen consumption and ventilation to carbon dioxide production ratio) from baseline to 2 weeks post last treatment. • Change in symptom status (NYHA class, Kansas City Cardiomyopathy questionnaire [KCCQ], visual analogue fatigue scale [VAFS]) from baseline to 2 weeks post treatment. • Change in haematological and biochemical indices (Hb, Hct, reticulocyte count, iron status, N-terminal brain natiuretic peptide [NT-BNP], cytokines and oxidative stress) from baseline to 2 weeks post treatment. • Change in cardiac function and tissue doppler indices on echocardiography. • Change in erythroid precursor and progenitor numbers on flow cytometry and cell culture. ;Timepoint(s) of evaluation of this end point: Endpoint will be evaluated at baseline and study end (2 weeks after last treatment) | — |
Countries
United Kingdom
Contacts
Public ContactDr Darlington Okonko
King's College London
Outcome results
None listed