Chronic Obstructive Pulmonary DiseasePhase 2ICE-TNCT03050424
Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial
A Phase 2 study testing Ferric Carboxymaltose and Sodium Chloride 0.9% in people with Chronic Obstructive Pulmonary Disease, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This phase II single centre, double blind, placebo-controlled, randomised trial aims to test the hypothesis that intravenous iron improves exercise performance in Chronic Obstructive Pulmonary Disease (COPD) as measured by constant rate cycle ergometry. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Ferric Carboxymaltose and Sodium Chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2017to 1 Jan 2019
- Phase
- Phase 2
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinically stable patients (>18 years old), Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV COPD Forced Expiratory Volume in 1 second (FEV1):Forced Vital capacity (FVC) < 0.70
- Non-anaemic: males haemoglobin (Hb) ≥ 130g/L, and females ≥ 120g/L
- Iron deficiency, defined as:
- Serum Ferritin < 100 µg/ml
- Serum Ferritin 100-299 µg/ml with Transferrin saturation (TSAT) < 16%
- Soluble transferring receptor > 28.1nmol/L
- No history of lower respiratory tract infection or exacerbation of COPD in the last 6 weeks
- No participation in Pulmonary Rehabilitation (PR) for at least 3 months prior to initial assessment.
Who cannot join
- Polycythemia defined as Hb > 170g/L and haematocrit > 0.6 in males and Hb > 150g/L and haematocrit > 0.56 in females.
- Significant co-morbidity contributing to reduced exercise tolerance
- Congestive cardiac failure defined as Left Ventricular Ejection Fraction (LVEF) < 45% or plasma B-type natriuretic peptide (BNP) > 100pg/ml.
- Oral iron therapy at doses > 100mg/day in the previous week prior to randomisation.
- Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of normal range.
- Anaemia (WHO [31]) defined as Hb < 130g/L in males > 15 yrs old and Hb < 120g/L in non-pregnant females.
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- Current malignancy or haematological disorders.
- Currently receiving systemic chemotherapy and/or radiotherapy.
- Renal dialysis (previous, current or planned).
- Unstable angina.
- Subject is of child-bearing potential or is pregnant or breast feeding.
- Contraindication to Ferrous Carboxymaltose (Ferinject):
- Hypersensitivity to active substance
- Known serious hypersensitivity to other parental iron substance
- Anaemia not attributed to iron deficiency (e.g. other microcytic anaemia)
- Evidence of iron overload or disturbance in utilisation of iron.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Brompton & Harefield NHS Foundation Trust
London, SW3 6HP
Matthew Pavitt, MBBS, MRCP
About this study
This phase II single centre, double blind, placebo-controlled, randomised trial aims to test the hypothesis that intravenous iron improves exercise performance in Chronic Obstructive Pulmonary Disease (COPD) as measured by constant rate cycle ergometry.
Read the detailed description
Iron deficiency (ID) is one of the most common nutritional deficiencies affecting humans. Chronic diseases, including COPD, are commonly complicated by iron deficiency anaemia (IDA). It has been well documented that there is an association between both ID and anaemia and reduced exercise capacity. It has been postulated that addressing this ID may be a novel approach to improve exercise capacity and quality of life.
The ECLIPSE cohort found that the prevalence of anaemia in patients with COPD is 19% and is associated with functional limitation and poor outcomes; similarly Nickol et al (2015) found ID to be prevalent in 17.7% of patients with COPD.
Barberan-Garcia et al (2015) evaluated the relationship between Non-anaemic iron deficiency (NAID) and aerobic capacity in seventy COPD patients before and after an 8 week high intensity endurance exercise training programme. Endurance time was assessed as endurance time during constant work rate exercise testing at 80% of oxygen consumption (VO2) peak. At baseline it was noted that the NAID group in comparison to the normal iron status group had a lower exercise tolerance of approximately 90 seconds, which is close to normally reported minimal clinical important difference (MCID's) for this test, P=0.007. After adjusting for confounding variables with a multiple regression analysis it was shown that training induced increase in aerobic exercise capacity was only found in the normal iron status group, with the effect of training on exercise tolerance being lower in the NAID (P=0.041).
Exercise capacity in COPD is strongly linked to outcome measures and mortality. The benefit of correcting NAID in COPD subjects would be to achieve an increase in exercise endurance and thus an improvement in Quality of Life (QoL). Currently there is no standard treatment for NAID in COPD, so this pilot, randomised, double-blind, placebo-controlled trial will attempt to answer this question.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Ferric Carboxymaltose, Sodium Chloride 0.9%
- Keywords
- COPD, Iron, Exercise Capacity, Non-anaemic iron deficiency
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric CarboxymaltoseDrug
Also called Ferinject®
Ferric Carboxymaltose injectable Product
Sodium Chloride 0.9%Drug
Sodium Chloride 0.9%
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | Ferric Carboxymaltose (FCM) (Ferinject) at 15 mg iron/kg body weight Receives: Drug: Ferric Carboxymaltose |
| Placebo | Placebo comparator | Sodium Chloride 0.9% Receives: Drug: Sodium Chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Constant Rate Cycle Ergometry (75% Max Load)
Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max
Measured: 8 weeks
Secondary outcomes (8)
Quality of Life
COPD Assessment Test (CAT)
Measured: Week 0; Week 8; Week 10; Week 14
Quality of Life
Medical Research Council (MRC) Dyspnoea Scale
Measured: Week 0; Week 8; Week 10; Week 14
Quality of Life
Hospital Anxiety and Depression (HAD) Scale
Measured: Week 0; Week 8; Week 10; Week 14
Quality of Life
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
Measured: Week 0; Week 8; Week 10; Week 14
Quality of Life
EuroQoL Group (EQ-5D-5L)
Measured: Week 0; Week 8; Week 10; Week 14
Muscle Oxygen Delivery
Near infrared spectroscopy during muscle contraction
Measured: Week 0; Week 8; Week 14
Endurance Shuttle Walk Test (ESWT)
Change in endurance shuttle walk test distance and time
Measured: Week 0; Week 4; Week 10; Week 14
Adverse Effects of Iron Administration
Any adverse effects of intravenous iron administration
Measured: Week 0; Week 4; Week 8; Week 10; Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2017
- Study start1 Apr 2017
- Primary completion1 Oct 2018 (estimated)
- Study completion1 Jan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Polkey, MRCP, PhD, Principal investigator, Royal Bromtpon and Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03050424
- Sponsor's protocol ID
- 2016LF003B
- Other IDs
- 2016-000829-39, 16/EE/0355, 2016
- Acronym
- ICE-T
- Status last verified
- May 2017
- First submitted
- 7 Feb 2017
- Last updated
- 12 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Demeyer H, Louvaris Z, Frei A, Rabinovich RA, de Jong C, Gimeno-Santos E, Loeckx M, Buttery SC, Rubio N, Van der Molen T, Hopkinson NS, Vogiatzis I, Puhan MA, Garcia-Aymerich J, Polkey MI, Troosters T; Mr Papp PROactive study group and the PROactive consortium. Physical activity is increased by a 12-week semiautomated telecoaching programme in patients with COPD: a multicentre randomised controlled trial. Thorax. 2017 May;72(5):415-423. doi: 10.1136/thoraxjnl-2016-209026. Epub 2017 Jan 30.
PubMed 28137918Zoumot Z, Davey C, Jordan S, McNulty WH, Carr DH, Hind MD, Polkey MI, Shah PL, Hopkinson NS. Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation: open label treatment following the BeLieVeR-HIFi study. Thorax. 2017 Mar;72(3):277-279. doi: 10.1136/thoraxjnl-2016-208865. Epub 2016 Dec 20.
PubMed 27999170Nolan CM, Maddocks M, Canavan JL, Jones SE, Delogu V, Kaliaraju D, Banya W, Kon SSC, Polkey MI, Man WD. Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2017 May 15;195(10):1344-1352. doi: 10.1164/rccm.201607-1372OC.
PubMed 27911566Demeyer H, Gimeno-Santos E, Rabinovich RA, Hornikx M, Louvaris Z, de Boer WI, Karlsson N, de Jong C, Van der Molen T, Vogiatzis I, Janssens W, Garcia-Aymerich J, Troosters T, Polkey MI; PROactive consortium. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used. PLoS One. 2016 Mar 14;11(3):e0151255. doi: 10.1371/journal.pone.0151255. eCollection 2016.
PubMed 26974332
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial
- ClinicalTrials.gov ID
- NCT03050424
- Acronym / sponsor ID
- ICE-T / 2016LF003B
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Iron, Exercise Capacity, Non-anaemic iron deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 1 Oct 2018 (estimated)
- Study completion
- 1 Jan 2019 (estimated)
- First posted
- 10 Feb 2017 (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 phase II single centre, double blind, placebo-controlled, randomised trial aims to test the hypothesis that intravenous iron improves exercise performance in Chronic Obstructive Pulmonary Disease (COPD) as measured by constant rate cycle ergometry.
Detailed description
Iron deficiency (ID) is one of the most common nutritional deficiencies affecting humans. Chronic diseases, including COPD, are commonly complicated by iron deficiency anaemia (IDA). It has been well documented that there is an association between both ID and anaemia and reduced exercise capacity. It has been postulated that addressing this ID may be a novel approach to improve exercise capacity and quality of life.
The ECLIPSE cohort found that the prevalence of anaemia in patients with COPD is 19% and is associated with functional limitation and poor outcomes; similarly Nickol et al (2015) found ID to be prevalent in 17.7% of patients with COPD.
Barberan-Garcia et al (2015) evaluated the relationship between Non-anaemic iron deficiency (NAID) and aerobic capacity in seventy COPD patients before and after an 8 week high intensity endurance exercise training programme. Endurance time was assessed as endurance time during constant work rate exercise testing at 80% of oxygen consumption (VO2) peak. At baseline it was noted that the NAID group in comparison to the normal iron status group had a lower exercise tolerance of approximately 90 seconds, which is close to normally reported minimal clinical important difference (MCID's) for this test, P=0.007. After adjusting for confounding variables with a multiple regression analysis it was shown that training induced increase in aerobic exercise capacity was only found in the normal iron status group, with the effect of training on exercise tolerance being lower in the NAID (P=0.041).
Exercise capacity in COPD is strongly linked to outcome measures and mortality. The benefit of correcting NAID in COPD subjects would be to achieve an increase in exercise endurance and thus an improvement in Quality of Life (QoL). Currently there is no standard treatment for NAID in COPD, so this pilot, randomised, double-blind, placebo-controlled trial will attempt to answer this question.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: Ferric CarboxymaltoseFerric Carboxymaltose (FCM) (Ferinject) at 15 mg iron/kg body weight |
| Placebo | Placebo comparator | Drug: Sodium Chloride 0.9%Sodium Chloride 0.9% |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Clinically stable patients (>18 years old), Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV COPD Forced Expiratory Volume in 1 second (FEV1):Forced Vital capacity (FVC) < 0.70
- Non-anaemic: males haemoglobin (Hb) ≥ 130g/L, and females ≥ 120g/L
- Iron deficiency, defined as:
- No history of lower respiratory tract infection or exacerbation of COPD in the last 6 weeks
- No participation in Pulmonary Rehabilitation (PR) for at least 3 months prior to initial assessment.
Key exclusion criteria (16 listed)
- Polycythemia defined as Hb > 170g/L and haematocrit > 0.6 in males and Hb > 150g/L and haematocrit > 0.56 in females.
- Significant co-morbidity contributing to reduced exercise tolerance
- Congestive cardiac failure defined as Left Ventricular Ejection Fraction (LVEF) < 45% or plasma B-type natriuretic peptide (BNP) > 100pg/ml.
- Oral iron therapy at doses > 100mg/day in the previous week prior to randomisation.
- Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of normal range.
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 |
|---|---|---|
| Ferric CarboxymaltoseAlso: Ferinject®Ferric Carboxymaltose injectable Product | Drug | Active |
| Sodium Chloride 0.9%Sodium Chloride 0.9% | Drug | Placebo |
Primary outcome
Constant Rate Cycle Ergometry (75% Max Load)
Time frame: 8 weeks
Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max
8 secondary outcomes
Quality of Life
Time frame: Week 0; Week 8; Week 10; Week 14
Quality of Life
Time frame: Week 0; Week 8; Week 10; Week 14
Quality of Life
Time frame: Week 0; Week 8; Week 10; Week 14
Quality of Life
Time frame: Week 0; Week 8; Week 10; Week 14
Quality of Life
Time frame: Week 0; Week 8; Week 10; Week 14
Muscle Oxygen Delivery
Time frame: Week 0; Week 8; Week 14
Endurance Shuttle Walk Test (ESWT)
Time frame: Week 0; Week 4; Week 10; Week 14
Adverse Effects of Iron Administration
Time frame: Week 0; Week 4; Week 8; Week 10; Week 14
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2017.
- Background: PubMed 28137918Demeyer H, Louvaris Z, Frei A, Rabinovich RA, de Jong C, Gimeno-Santos E, Loeckx M, Buttery SC, Rubio N, Van der Molen T, Hopkinson NS, Vogiatzis I, Puhan MA, Garcia-Aymerich J, Polkey MI, Troosters T; Mr Papp PROactive study group and the PROactive consortium. Physical activity is increased by a 12-week semiautomated telecoaching programme in patients with COPD: a multicentre randomised controlled trial. Thorax. 2017 May;72(5):415-423. doi: 10.1136/thoraxjnl-2016-209026. Epub 2017 Jan 30.
- Background: PubMed 27999170Zoumot Z, Davey C, Jordan S, McNulty WH, Carr DH, Hind MD, Polkey MI, Shah PL, Hopkinson NS. Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation: open label treatment following the BeLieVeR-HIFi study. Thorax. 2017 Mar;72(3):277-279. doi: 10.1136/thoraxjnl-2016-208865. Epub 2016 Dec 20.
- Background: PubMed 27911566Nolan CM, Maddocks M, Canavan JL, Jones SE, Delogu V, Kaliaraju D, Banya W, Kon SSC, Polkey MI, Man WD. Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2017 May 15;195(10):1344-1352. doi: 10.1164/rccm.201607-1372OC.
- Background: PubMed 26974332Demeyer H, Gimeno-Santos E, Rabinovich RA, Hornikx M, Louvaris Z, de Boer WI, Karlsson N, de Jong C, Van der Molen T, Vogiatzis I, Janssens W, Garcia-Aymerich J, Troosters T, Polkey MI; PROactive consortium. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used. PLoS One. 2016 Mar 14;11(3):e0151255. doi: 10.1371/journal.pone.0151255. eCollection 2016.
- Drug information for Sodium Chloride Injection BP 0.9% w/vLink provided by the sponsor.
- Drug information for Ferinject (ferric carboxymaltose)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Michael Polkey, MRCP, PhD principal investigator
Royal Bromtpon and Harefield 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 2 study testing Ferric Carboxymaltose and Sodium Chloride 0.9% in people with Chronic Obstructive Pulmonary Disease, run by Royal Brompton & Harefield NHS Foundation 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 8 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 12 May 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matthew Pavitt, MBBS, MRCP (0207 351 8029, M.Pavitt@rbht.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Constant Rate Cycle Ergometry (75% Max Load) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03050424, which also lists 4 linked publications.
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 12 May 2017.