CKD Stage 3Phase 4NCT04862715
The Iron and Muscle Study
A Phase 4 study testing Ferinject in people with CKD Stage 3 and CKD Stage 4, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial summary
This is a multi-center randomized controlled trial that will examine the efficacy of IV iron supplementation when compared to placebo, with and without exercise training, on changes in patient exercise capacity. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- CKD Stage 3, CKD Stage 4, Iron-deficiency
- What is being tested?
- Ferinject
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Apr 2019to 21 Feb 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with established CKD (Stages 3-4) not on dialysis
- Resting BP ≤ 160/95mmHg
- Men and women aged 18 - 80 years
- Serum ferritin level less than 100μg/L AND/OR transferrin saturation ≤20%
- Haemoglobin 110 - 150 g/L
Who cannot join
- Pregnancy or breast feeding (Female patients of childbearing age will be asked if there is any possibility they may be pregnant. This is standard of care and no pregnancy test will be requested unless there is doubt about this. IV iron is given to many pregnant patients in standard treatment and there is no evidence of harm to mother or foetus).
- Weight < 50kg
- Known allergy to iron therapy
- Haemochromatosis, porphyria cutanea tarda or history of acquired iron overload
- Intravenous iron within previous 6 weeks
- CRP > 50 mg/L
Show all 22Show fewer
- Serum phosphate < 0.7 mmol/L.
- Active infection
- Current therapy with ESAs
- Uncontrolled atrial fibrillation
- Use of anticoagulants in those under consideration for muscle biopsy
- Unstable angina or heart attack within the last year
- Presence of solid organ cancer
- Known haemoglobinopathy, myelodysplasia, or myeloma
- Patients with peripheral vascular or musculoskeletal disease, who the investigator deems unable to carry out the 6MWT.
- Known severe aortic stenosis and pacemaker in-situ
- History of severe atopy
- Severe liver disease with serum transaminases > x3 upper limit of normal range according to local laboratory values.
- Severe lung disease with FEV1 known to be <50% predicted in last year
- Known heart failure with a left ventricular ejection fraction <45% in last year
- Any other health condition considered by the local Principal Investigator in which IV iron will be contraindicated.
- Insufficient understanding of the trial
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
King's College Hospital NHS Foundation Trust
London, SE5 9RS
About this study
Official title: Multicentre Prospective Double-blind Randomised Controlled Trial of the Effect of Intravenous Iron Supplementation and Exercise Training in Iron-deficient, But Not Anaemic, Patients With Chronic Kidney Disease on Exercise Capacity, Physical Function, Fatigue, and Skeletal Muscle Metabolism
This is a multi-center randomized controlled trial that will examine the efficacy of IV iron supplementation when compared to placebo, with and without exercise training, on changes in patient exercise capacity. The study aims to provide sufficient data to inform a power calculation for the definitive study to examine whether IV iron therapy in patients with CKD stages 3-4 (non-dialysis) can improve exercise capacity, muscle metabolism and physical function. Specifically, we propose to examine whether a strategy of IV iron therapy in patients with stages 3-4 CKD who are iron-deficient but NOT anaemic leads to improvements in exercise capacity.
Very little is currently known about the effects of iron deficiency on cardiac or skeletal muscle metabolism in patients suffering from CKD. Nevertheless, it seems likely that iron deficiency will contribute to mitochondrial dysfunction and reduced energy production in cardiac or skeletal muscle of CKD patients, and importantly may contribute to the reduced exercise capacity, physical function and overwhelming fatigue commonly reported in this population. The results of this trial will provide data to ascertain whether intravenous iron therapy might be beneficial to exercise capacity, muscle metabolism, physical function, and fatigue and whether iron repletion enhances the effect of an exercise intervention.
- Conditions
- CKD Stage 3, CKD Stage 4, Iron-deficiency
- Being tested
- Ferinject, Placebo: NaCl (sodium chloride 0.9%)
- Medical subject headings
- Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerinjectDrug
Active study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose.
Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited
Placebo: NaCl (sodium chloride 0.9%)Other
Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Active comparator | Active study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose.
Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited Receives: Drug: Ferinject |
| Placebo | Placebo comparator | Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier Receives: Other: Placebo: NaCl (sodium chloride 0.9%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exercise capacity as measured by 6 minute walk distance (6MWD)
An exercise capacity test
Measured: 4 weeks
Secondary outcomes (13)
Haemoglobin levels
Haemoglobin
Measured: 12 weeks
Iron status
Ferritin
Measured: 12 weeks
Renal function
urea,
Measured: 12 weeks
VO2 peak test (in a sub-set of participants)
To assess physical capacity
Measured: 12 weeks
Isokinetic dynamometry (muscle strength)
To assess physical capacity
Measured: 12 weeks
Functional capacity
sit-to-stand 60 to assess lower limb function
Measured: 12 weeks
KDQOL-36
To assess quality of life by classifying patient general state of health. 1 - Excellent, 2 - Very Good, 3 - Good, 4 - Fair, 5 - Poor.
Measured: 12 weeks
Skeletal muscle phosphocreatine recovery halftime (PCr t1/2) on MRI spectroscopy (n=40 patients at baseline and 4 weeks)
To assess skeletal muscle metabolism
Measured: 12 weeks
The Work and Social Adjustment Scale (WSAS)
To assess quality of life by classifying out more about how participant fatigue impacts on their daily life 0 - Not at all, 1 to 2 - Slightly, 3 to 4 - Definitely, 5 to 6 - markedly and 7 to 8 - Very severely impaired /Cannot work
Measured: 12 weeks
To assess the impact of iron regulatory genes e.g. HFE, TMPRSS6 etc. on the primary and secondary endpoints of the study (exploratory only)
Patients will be asked if they are willing to provide DNA from a single sample of whole blood to facilitate analysis of up to 90 iron regulatory genes, including HFE and TMPRSS. Iron regulatory gene expression measured by qPCR e.g. Hepcidin, Hemojuvelin, Ferroportin, Trf1 receptor, and iron regulatory proteins-1 \& -2.
Measured: 12 Weeks
Iron Status
TSAT
Measured: 12 weeks
Renal Function
creatinine
Measured: 12 weeks
Renal Function
estimated glomerular filtration rate to be used to determine renal function
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start26 Apr 2019
- Primary completion21 Dec 2021
- Study completion21 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CKD Stage 3Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London, University of Leicester
- Responsible party
- Sponsor
- Investigators
- Kate Bramham, Principal investigator, Kings College Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04862715
- Sponsor's protocol ID
- 234820
- Status last verified
- Feb 2022
- First submitted
- 3 Apr 2019
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre Prospective Double-blind Randomised Controlled Trial of the Effect of Intravenous Iron Supplementation and Exercise Training in Iron-deficient, But Not Anaemic, Patients With Chronic Kidney Disease on Exercise Capacity, Physical Function, Fatigue, and Skeletal Muscle Metabolism
- ClinicalTrials.gov ID
- NCT04862715
- Acronym / sponsor ID
- 234820
- Conditions
- CKD Stage 3, CKD Stage 4, Iron-deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London, University of Leicester
- Study start
- 26 Apr 2019 (actual)
- Primary completion
- 21 Dec 2021 (actual)
- Study completion
- 21 Feb 2022 (actual)
- First posted
- 28 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center randomized controlled trial that will examine the efficacy of IV iron supplementation when compared to placebo, with and without exercise training, on changes in patient exercise capacity. The study aims to provide sufficient data to inform a power calculation for the definitive study to examine whether IV iron therapy in patients with CKD stages 3-4 (non-dialysis) can improve exercise capacity, muscle metabolism and physical function. Specifically, we propose to examine whether a strategy of IV iron therapy in patients with stages 3-4 CKD who are iron-deficient but NOT anaemic leads to improvements in exercise capacity.
Very little is currently known about the effects of iron deficiency on cardiac or skeletal muscle metabolism in patients suffering from CKD. Nevertheless, it seems likely that iron deficiency will contribute to mitochondrial dysfunction and reduced energy production in cardiac or skeletal muscle of CKD patients, and importantly may contribute to the reduced exercise capacity, physical function and overwhelming fatigue commonly reported in this population. The results of this trial will provide data to ascertain whether intravenous iron therapy might be beneficial to exercise capacity, muscle metabolism, physical function, and fatigue and whether iron repletion enhances the effect of an exercise intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: FerinjectActive study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose. Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited |
| Placebo | Placebo comparator | Other: Placebo: NaCl (sodium chloride 0.9%)Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with established CKD (Stages 3-4) not on dialysis
- Resting BP ≤ 160/95mmHg
- Men and women aged 18 - 80 years
- Serum ferritin level less than 100μg/L AND/OR transferrin saturation ≤20%
- Haemoglobin 110 - 150 g/L
Key exclusion criteria (22 listed)
- Pregnancy or breast feeding (Female patients of childbearing age will be asked if there is any possibility they may be pregnant. This is standard of care and no pregnancy test will be requested unless there is doubt about this. IV iron is given to many pregnant patients in standard treatment and there is no evidence of harm to mother or foetus).
- Weight < 50kg
- Known allergy to iron therapy
- Haemochromatosis, porphyria cutanea tarda or history of acquired iron overload
- Intravenous iron within previous 6 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FerinjectActive study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose. Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited | Drug | Treatment |
| Placebo: NaCl (sodium chloride 0.9%)Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier | Other | Placebo |
Primary outcome
Exercise capacity as measured by 6 minute walk distance (6MWD)
Time frame: 4 weeks
An exercise capacity test
13 secondary outcomes
Haemoglobin levels
Time frame: 12 weeks
Iron status
Time frame: 12 weeks
Renal function
Time frame: 12 weeks
VO2 peak test (in a sub-set of participants)
Time frame: 12 weeks
Isokinetic dynamometry (muscle strength)
Time frame: 12 weeks
Functional capacity
Time frame: 12 weeks
KDQOL-36
Time frame: 12 weeks
Skeletal muscle phosphocreatine recovery halftime (PCr t1/2) on MRI spectroscopy (n=40 patients at baseline and 4 weeks)
Time frame: 12 weeks
The Work and Social Adjustment Scale (WSAS)
Time frame: 12 weeks
To assess the impact of iron regulatory genes e.g. HFE, TMPRSS6 etc. on the primary and secondary endpoints of the study (exploratory only)
Time frame: 12 Weeks
Iron Status
Time frame: 12 weeks
Renal Function
Time frame: 12 weeks
Renal Function
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kate Bramham principal investigator
Kings College Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ferinject in people with CKD Stage 3 and CKD Stage 4, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exercise capacity as measured by 6 minute walk distance (6MWD) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.