Condition category
Circulatory System
Date applied
06/06/2014
Date assigned
15/08/2014
Last edited
15/08/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Anaemia occurs in up to 30% of heart failure patients. A deficiency in iron is a common cause of anaemia in heart failure. Studies have shown anaemia to be an independent risk factor for death and hence there has been much interest in finding out the possible role of treating iron deficiency in improving outcomes. The answers are not clear as large studies are needed. The mechanism of anaemia and iron deficiency in heart failure is not fully understood. In particular, it is unknown what happens to iron levels when someone with heart failure gets admitted to hospital with excess fluid requiring treatment with drugs given through the vein (intravenous). Whether a potential iron deficiency detected when unwell gets better with time and whether this has any impact is unclear. This study will find out the mechanism of anaemia and iron deficiency in patients with heart failure.

Who can participate?
We will recruit 100 patients admitted to the participating hospital with heart failure needing intravenous treatment with diuretics (water tablets). We will compare our findings to a control group of participants with heart failure but who have not had a hospital admission for 3 months and 20 healthy individuals with no medical conditions requiring treatment.

What does the study involve?
For participants admitted to hospital with heart failure:
We will collect information on age, gender, medical conditions and medication details. We will perform an ECG, an echocardiogram (ultrasound scan of the heart) and carry out blood tests. The blood tests will be performed at the earliest opportunity after admission to hospital and will be repeated 24 hours prior to being discharged home. Blood tests are frequently performed (often on a daily basis) during hospital stay and where possible, we would aim to order our additional specialist tests on the same samples. This may involve having to withdraw an additional 15 ml of blood during routine blood test sampling. Before being discharged from hospital the participant will be asked to fill in a quality of life questionnaire and do a 6-minute walk test (a test often used to assess the functional status of heart failure patients that would involve assessing how far and how comfortably the participant can walk during a 6-minute period). Participation in the study will last 12 months, although no follow-up visits will be required after 3 months. There will be two clinic visits after discharge form hospital, at 4 weeks and 12 weeks after discharge from hospital. At each of these follow-up visits, the blood tests, ECG and 6-minute walk test will be repeated and the participant will be required to fill in the quality of life questionnaire.

For stable participants:
There will be two visits involved, 3 months apart. At the first visit, we will collect information on age, gender, medical conditions and medication details. We will perform an ECG, an echocardiogram (ultrasound scan of the heart) and do some blood tests. The participant will also be required to fill in a quality of life questionnaire and do a 6-minute walk test. At the second visit, we will repeat the blood tests, ECG, 6-minute walk test and the participant will be required to fill in the quality of life questionnaire again.

For healthy participants:
There will be a single visit where we will collect information on age, gender, medical conditions and medication details. We will perform an ECG, an echocardiogram (ultrasound scan of the heart) and do some blood tests. The participant will also be required to do a 6-minute walk test.

Every participant’s general practitioner (GP) will be informed of their participation and we will contact the GP 12 months into the study via telephone for information regarding hospitalizations or any other medical events in the interim.

What are the possible benefits and risks of participating?
There is no new treatment involved and as such there are no changes to routine clinical care. While there is no assurance that the participant will immediately benefit from this study, whatever information we gather will be highly beneficial to our understanding of the research subject and we hope will ultimately lead to better management of anaemia and iron deficiency in patients with heart failure. The risks are very minimal as there are no new treatments involved. All blood tests will be performed by highly skilled personnel to minimize whatever potential discomfort this could cause.

Where is the study run from?
The study will take place at Queen Alexandra Hospital, Cosham, Portsmouth, UK. All clinics will be held at the Cardiology department in the hospital.

When is the study starting and how long is it expected to run for?
The study started in February 2014 and will run for a year.

Who is funding the study?
Alere International (UK).

Who is the main contact?
Ms Charlotte Turner
charlotte.turner@porthosp.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Charlotte Turner

ORCID ID

Contact details

Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16223

Study information

Scientific title

Iron Status In Decompensated Heart Failure (IRON STATS-DHF) - an observational study aimed at assessing the prevalence of iron deficiency in decompensated heart failure and prospectively evaluating the change in iron status and association with renal function/inflammatory mediators with clinical improvement

Acronym

IRON STATS-DHF

Study hypothesis

Our study will focus on acute decompensated heart failure (ADHF) with the hypothesis that:
1. Iron deficiency is common in acute decompensated heart failure (ADHF).
2. Iron deficiency in ADHF is related to inflammatory immune activation and upregulation of hepcidin.
3. Iron deficiency at discharge from hospital following a decompensation, regardless of subsequent variations, will be a predictor of death and cardiovascular hospitalization (primary diagnosis of arrhythmia, ADHF or myocardial infarction) in the 12 months from original recruitment to the study.
4. Following ADHF, serum transferrin saturation (a marker of iron deficiency) is reduced at 4 weeks post discharge as a consequence of inflammatory immune activation and impaired renal function (even though ‘recompensation’ has occurred).

Additional objectives:
To enhance our understanding of the dynamic relationship between ADHF, alterations in inflammatory immune activation, renal function and iron deficiency, we would be comparing the various blood parameters in the ADHF cohort at discharge from hospital, as well as at 4 weeks and 12 weeks from discharge. A comparison would also be made with a stable chronic heart failure cohort. We foresee a persistent dip in iron levels in the ADHF cohort that does not recover to baseline despite recompensation.

Ethics approval

NRES Committee South Central, Portsmouth; 29/11/2012; ref. 12/SC/0536

Study design

Non-randomised; Observational; Design type: Cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Heart Failure

Intervention

Blood sampling, ECG, 6MWT. In addition to blood sampling on each study visit, participants will have to fill in a Kansas city cardiomyopathy questionnaire and have an ECG. Some visits will require an echocardiogram.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Prevalence of iron deficiency (absolute and functional) in acute decompensated heart failure
2. Change in iron status (transferrin saturation) at 4 and 12 weeks

Secondary outcome measures

1. Is iron deficiency independently predicted by:
1.1. Haemoglobin level
1.2. Hepcidin level
1.3. Renal function using serum creatinine
1.4. Serum urate
1.5. Inflammatory markers (C-reactive protein (CRP), Interleukin [IL] -1, IL-6)
1.6. Biomarkers of heart failure (B-natriuretic peptide [BNP]) and renal function (N-gal)
1.7. Right heart pressures assessed on trans-thoracic echocardiogram
1.8. Fluid loss during inpatient stay (assessed from daily weight charts maintained during in-patient stay)
1.9. 6-Minute Walk Test (6MWT) performed as per American Thoracic Society guidelines
1.10. Quality of Life assessed by using The Kansas City Cardiomyopathy Questionnaire (KCCQ)
2. Compare prevalence of iron deficiency between patients in systolic heart failure (LVEF <45%) vs diastolic heart failure and atrial fibrillation vs sinus rhythm.
3. Using a multivariate model and logistic regression analysis, we will ascertain whether the changes in iron status (change in transferrin saturation) post discharge from hospital are independently related to:
3.1. Blood parameters (haemoglobin, hepcidin, renal function, urate, inflammatory markers [CRP, TNF- α, IL-1 and IL-6], biomarkers BNP, N-gal)
3.2. Right heart pressures assessed on trans-thoracic echocardiogram
3.3. Fluid loss during inpatient stay
3.4. 6-Minute Walk Test (6MWT)
3.5. QOL assessed by using The Kansas City Cardiomyopathy Questionnaire
3.6. Presence of systolic (LVEF <45%) or diastolic heart failure
4. We will additionally assess prognosis defined as outcomes at 1 year (death and hospitalisation) in:
4.1. ADHF patients with iron deficiency vs no iron deficiency
4.2. ADHF patients with iron deficiency vs stable CHF patients with iron deficiency

Overall trial start date

18/02/2014

Overall trial end date

16/02/2015

Reason abandoned

Eligibility

Participant inclusion criteria

Study arm - acute decompensated heart failure (ADHF) patients:
1. Patients admitted with acute decompensated heart failure (defined as symptoms and signs secondary to abnormal cardiac function with weight gain of more than 3 kg above target weight or requiring intravenous diuretics for >48 hours).
2. Patients should be able to give informed consent.

Control arm - patients with stable heart failure:
1. There should be a prior diagnosis of CHF based on the presence of signs and symptoms of heart failure with objective evidence of a structural or functional abnormality of the heart at rest.
2. Patients should already be established on therapy, i.e. diuretics if required, ACE inhibitors/ARBs, beta blockers and aldosterone antagonists.
3. They should not have had a hospitalisation in the last 3 months.

Control arm - healthy age-matched particpants:
1. There should be no known cardiac abnormality or history of anaemia or iron deficiency.
2. They should not have any chronic conditions requiring aspirin, beta blockers, ACE inhibitors, ARBs or aldosterone antagonist therapy in the last 3 months.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 150; UK Sample Size: 150

Participant exclusion criteria

1. Patients less than 18 years of age
2. Patients who are part of any other ongoing research study
3. Hospitalisation for stable heart failure or age-matched control patient in the last 3 months

Recruitment start date

18/02/2014

Recruitment end date

16/02/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Sponsor information

Organisation

Portsmouth Hospitals NHS Trust (UK)

Sponsor details

Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Alere International (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes