Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial

Background Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension. We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capa...

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Main Authors: Nayia Petousi, Nick P Talbot, Peter A Robbins, Mona Bafadhel, Annabel H Nickol, Peter Santer, Matthew C Frise, Anne McGahey, Richard Baskerville
Format: Article
Language:English
Published: BMJ Publishing Group 2020-09-01
Series:BMJ Open Respiratory Research
Online Access:https://bmjopenrespres.bmj.com/content/7/1/e000577.full
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author Nayia Petousi
Nick P Talbot
Peter A Robbins
Mona Bafadhel
Annabel H Nickol
Peter Santer
Matthew C Frise
Anne McGahey
Richard Baskerville
author_facet Nayia Petousi
Nick P Talbot
Peter A Robbins
Mona Bafadhel
Annabel H Nickol
Peter Santer
Matthew C Frise
Anne McGahey
Richard Baskerville
author_sort Nayia Petousi
collection DOAJ
description Background Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension. We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD).Methods We performed a randomised, placebo-controlled, double-blind trial in 48 participants with COPD (mean±SD: age 69±8 years, haemoglobin 144.8±13.2 g/L, ferritin 97.1±70.0 µg/L, transferrin saturation 31.3%±15.2%; GOLD grades II–IV), each of whom received a single dose of intravenous ferric carboxymaltose (FCM; 15 mg/kg bodyweight) or saline placebo. The primary endpoint was peripheral oxygen saturation (SpO2) at rest after 1 week. The secondary endpoints included daily SpO2, overnight SpO2, exercise SpO2, 6 min walk distance, symptom and quality of life scores, serum iron indices, spirometry, echocardiographic measures, and exacerbation frequency.Results SpO2 was unchanged 1 week after FCM administration (difference between groups 0.8%, 95% CI −0.2% to 1.7%). However, in secondary analyses, exercise capacity increased significantly after FCM administration, compared with placebo, with a mean difference in 6 min walk distance of 12.6 m (95% CI 1.6 to 23.5 m). Improvements of ≥40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after 1 week (p=0.009). Modified MRC Dyspnoea Scale score was also significantly lower after FCM, and fewer participants reported scores ≥2 in the FCM group, compared with placebo (33.3% vs 66.7%, p=0.02). No significant differences were observed in other secondary endpoints. Adverse event rates were similar between groups, except for hypophosphataemia, which occurred more frequently after FCM (91.7% vs 8.3%, p<0.001).Conclusions FCM did not improve oxygenation over 8 weeks in patients with COPD. However, this treatment was well tolerated and produced improvements in exercise capacity and functional limitation caused by breathlessness. These effects on secondary endpoints require confirmation in future studies.Trial registration number ISRCTN09143837.
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spelling doaj-art-d3152b52eb28409f8a8380b35a0c1c2f2025-08-20T02:22:25ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392020-09-017110.1136/bmjresp-2020-000577Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trialNayia Petousi0Nick P Talbot1Peter A Robbins2Mona Bafadhel3Annabel H Nickol4Peter Santer5Matthew C Frise6Anne McGahey7Richard Baskerville8Nuffield Department of Medicine, University of Oxford, Oxford, UKOxford NIHR Respiratory Biomedical Research Centre, University of Oxford, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK2 Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK4 Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK1 Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USADepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UKOxford Respiratory Trials Unit, University of Oxford, Oxford, UKNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UKBackground Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension. We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD).Methods We performed a randomised, placebo-controlled, double-blind trial in 48 participants with COPD (mean±SD: age 69±8 years, haemoglobin 144.8±13.2 g/L, ferritin 97.1±70.0 µg/L, transferrin saturation 31.3%±15.2%; GOLD grades II–IV), each of whom received a single dose of intravenous ferric carboxymaltose (FCM; 15 mg/kg bodyweight) or saline placebo. The primary endpoint was peripheral oxygen saturation (SpO2) at rest after 1 week. The secondary endpoints included daily SpO2, overnight SpO2, exercise SpO2, 6 min walk distance, symptom and quality of life scores, serum iron indices, spirometry, echocardiographic measures, and exacerbation frequency.Results SpO2 was unchanged 1 week after FCM administration (difference between groups 0.8%, 95% CI −0.2% to 1.7%). However, in secondary analyses, exercise capacity increased significantly after FCM administration, compared with placebo, with a mean difference in 6 min walk distance of 12.6 m (95% CI 1.6 to 23.5 m). Improvements of ≥40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after 1 week (p=0.009). Modified MRC Dyspnoea Scale score was also significantly lower after FCM, and fewer participants reported scores ≥2 in the FCM group, compared with placebo (33.3% vs 66.7%, p=0.02). No significant differences were observed in other secondary endpoints. Adverse event rates were similar between groups, except for hypophosphataemia, which occurred more frequently after FCM (91.7% vs 8.3%, p<0.001).Conclusions FCM did not improve oxygenation over 8 weeks in patients with COPD. However, this treatment was well tolerated and produced improvements in exercise capacity and functional limitation caused by breathlessness. These effects on secondary endpoints require confirmation in future studies.Trial registration number ISRCTN09143837.https://bmjopenrespres.bmj.com/content/7/1/e000577.full
spellingShingle Nayia Petousi
Nick P Talbot
Peter A Robbins
Mona Bafadhel
Annabel H Nickol
Peter Santer
Matthew C Frise
Anne McGahey
Richard Baskerville
Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
BMJ Open Respiratory Research
title Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
title_full Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
title_fullStr Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
title_full_unstemmed Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
title_short Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial
title_sort intravenous iron and chronic obstructive pulmonary disease a randomised controlled trial
url https://bmjopenrespres.bmj.com/content/7/1/e000577.full
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