Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial (ICE-T)

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Ferric Carboxymaltose; Drug: Sodium Chloride 0.9%

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6HP
    • Recruiting
    • Royal Brompton & Harefield NHS Foundation Trust
    • Contact: Matthew Pavitt, MBBS, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Non-anaemic: males haemoglobin (Hb) ≥ 130g/L, and females ≥ 120g/L

3. Iron deficiency, defined as:

   1. Serum Ferritin < 100 µg/ml
   2. Serum Ferritin 100-299 µg/ml with Transferrin saturation (TSAT) < 16%
   3. Soluble transferring receptor > 28.1nmol/L
4. No history of lower respiratory tract infection or exacerbation of COPD in the last 6 weeks
5. No participation in Pulmonary Rehabilitation (PR) for at least 3 months prior to initial assessment.

Exclusion Criteria:

1. Polycythemia defined as Hb > 170g/L and haematocrit > 0.6 in males and Hb > 150g/L and haematocrit > 0.56 in females.
2. Significant co-morbidity contributing to reduced exercise tolerance
3. Congestive cardiac failure defined as Left Ventricular Ejection Fraction (LVEF) < 45% or plasma B-type natriuretic peptide (BNP) > 100pg/ml.
4. Oral iron therapy at doses > 100mg/day in the previous week prior to randomisation.
5. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of normal range.
6. Anaemia (WHO [31]) defined as Hb < 130g/L in males > 15 yrs old and Hb < 120g/L in non-pregnant females.
7. Current malignancy or haematological disorders.
8. Currently receiving systemic chemotherapy and/or radiotherapy.
9. Renal dialysis (previous, current or planned).
10. Unstable angina.
11. Subject is of child-bearing potential or is pregnant or breast feeding.

12. Contraindication to Ferrous Carboxymaltose (Ferinject):

    1. Hypersensitivity to active substance
    2. Known serious hypersensitivity to other parental iron substance
    3. Anaemia not attributed to iron deficiency (e.g. other microcytic anaemia)
    4. Evidence of iron overload or disturbance in utilisation of iron.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Sodium Chloride 0.9%	Drug: Sodium Chloride 0.9%; Sodium Chloride 0.9%
Experimental: Active; Ferric Carboxymaltose (FCM) (Ferinject) at 15 mg iron/kg body weight	Drug: Ferric Carboxymaltose; Ferric Carboxymaltose injectable Product; Other Names: Ferinject®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Constant Rate Cycle Ergometry (75% Max Load)	Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	COPD Assessment Test (CAT)	Week 0; Week 8; Week 10; Week 14
Quality of Life	Medical Research Council (MRC) Dyspnoea Scale	Week 0; Week 8; Week 10; Week 14
Quality of Life	Hospital Anxiety and Depression (HAD) Scale	Week 0; Week 8; Week 10; Week 14
Quality of Life	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)	Week 0; Week 8; Week 10; Week 14
Quality of Life	EuroQoL Group (EQ-5D-5L)	Week 0; Week 8; Week 10; Week 14
Muscle Oxygen Delivery	Near infrared spectroscopy during muscle contraction	Week 0; Week 8; Week 14
Endurance Shuttle Walk Test (ESWT)	Change in endurance shuttle walk test distance and time	Week 0; Week 4; Week 10; Week 14
Adverse Effects of Iron Administration	Any adverse effects of intravenous iron administration	Week 0; Week 4; Week 8; Week 10; Week 14

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: Michael Polkey, MRCP, PhD, Royal Bromtpon and Harefield NHS Foundation Trust

Publications and helpful links

General Publications

• Zoumot 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.
• 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.
• Nolan 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.
• Demeyer 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.

Helpful Links

• Drug information for Sodium Chloride Injection BP 0.9% w/v
• Drug information for Ferinject (ferric carboxymaltose)

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Actual): February 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Iron; Exercise Capacity; Non-anaemic iron deficiency
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2016LF003B; 2016-000829-39 (EudraCT Number); 16/EE/0355 (Other Identifier: REC Reference)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No