Clinical Trial Results:
Mechanisms of Exercise Benefit with Intravenous Iron in Chronic Heart Failure: The Ferric Iron in Heart Failure (FERRIC HF) II Trial
|
Summary
|
|
EudraCT number |
2012-005592-13 |
Trial protocol |
GB |
Global end of trial date |
20 Dec 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
21 Mar 2019
|
First version publication date |
21 Mar 2019
|
Other versions |
|
Summary report(s) |
FINAL STUDY REPORT |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
FERRICHFII
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
King's College London
|
||
Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
|
||
Public contact |
Dr Darlington Okonko, King's College London, 0044 207848 5017, darlington.okonko@kcl.ac.uk
|
||
Scientific contact |
Dr Darlington Okonko, King's College London, 0044 207848 5017, darlington.okonko@kcl.ac.uk
|
||
Sponsor organisation name |
King's College Hospital
|
||
Sponsor organisation address |
Denmark Hill, London, United Kingdom, SE59RS
|
||
Public contact |
Dr Darlington Okonko, King's College NHS Foundation Trust, 0044 207848 5017, darlington.okonko@kcl.ac.uk
|
||
Scientific contact |
Dr Darlington Okonko, King's College NHS Foundation Trust, 0044 207848 5017, darlington.okonko@kcl.ac.uk
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
20 Dec 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
20 Dec 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Dec 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
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.
|
||
Protection of trial subjects |
Number and incidence of adverse events; changes in liver function tests and renal function tests; changes in vital parameters will be recorded throughout the study.
|
||
Background therapy |
Participants will be receiving optimal conventional therapy for at least 4 weeks prior to recruitment and without dose changes for at least 2 weeks. | ||
Evidence for comparator |
not applicable | ||
Actual start date of recruitment |
07 Jan 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 40
|
||
Worldwide total number of subjects |
40
|
||
EEA total number of subjects |
40
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
16
|
||
From 65 to 84 years |
23
|
||
85 years and over |
1
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Participants were recruited from one clinical site within the UK, between 2014 and 2016. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
≥30 years of age, 50% anaemic and 50% non-anaemic participants with CHF. The study consists of a screening (week -1 to -4) and baseline assessment period (week 0), followed by a baseline assessment and first treatment phase (day 0 of week 0), | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall Trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Blinding implementation details |
Blinding will be achieved by shielding the infusion arm from patients and using opaque iv giving sets
|
|||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
IV IRON | |||||||||
Arm description |
Stratified Randomisation (Anaemia defined as Hb<12 in females and <13 in males) 10 anaemic participants and 10 non anaemic participants will receive Monofer Infusion at week 0 (and week 1 if dose ≥ 20 mg iron/kg | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Monofer 100 mg/ml solution for injection/infusion
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Solution for solution for infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
In patients randomised to total dose iv iron infusion, the repletion dose will be calculated by the following Ganzoni equation and rounded up to the nearest multiple of 100mg:
body weight (kg) x 2.4 x (15- patients haemoglobin [g/dl]) + 500 mg (for stores), administered at week 0 (and week 1 if dose
≥ 20 mg iron/kg
|
|||||||||
|
Arm title
|
PLACEBO | |||||||||
Arm description |
Stratified Randomisation (Anaemia defined as Hb<12 in females and <13 in males) 10 anaemic participants and 10 non anaemic participants will receive Normal Saline Infusion at week 0 (and week 1 if dose ≥ 20 mg iron/kg | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
0.9% Normal Saline
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Solution for solution for infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
Patients randomised to the placebo group will have their total iron repletion dose calculated using the Ganzoni formula as detailed for the IRON group and their infusion duration worked out. These subjects will receive 100ml of sterile 0.9% sodium chloride over their respective infusion periods in a resuscitation area with blood pressure monitoring as above.
|
|||||||||
|
||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
IV IRON
|
||
Reporting group description |
Stratified Randomisation (Anaemia defined as Hb<12 in females and <13 in males) 10 anaemic participants and 10 non anaemic participants will receive Monofer Infusion at week 0 (and week 1 if dose ≥ 20 mg iron/kg | ||
Reporting group title |
PLACEBO
|
||
Reporting group description |
Stratified Randomisation (Anaemia defined as Hb<12 in females and <13 in males) 10 anaemic participants and 10 non anaemic participants will receive Normal Saline Infusion at week 0 (and week 1 if dose ≥ 20 mg iron/kg | ||
|
||||||||||
End point title |
Change in skeletal muscle oxidative capacity [1] | |||||||||
End point description |
Change in skeletal muscle oxidative capacity as assessed by PCr t1/2 from baseline to 2 weeks post last treatment
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Until 2 weeks post last treatment/infusion
|
|||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see attached charts and documents for results. |
||||||||||
|
||||||||||
Attachments |
Results Tables |
|||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Secondary Endpoints | |||||||||
End point description |
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
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From baseline to two weeks post treatment/infusion
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Safety | |||||||||
End point description |
Number and incidence of adverse events; changes in liver function tests and renal function tests; changes in vital parameters.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline until completion of trial.
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Enrolement until trial completion.
|
||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IV IRON GROUP
|
||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO GROUP
|
||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
10 Sep 2015 |
1)Change of folate in inclsuion 2) Change of exclusion critera (NSA study duration) |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
