ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12618000185268

Ethics application status

Approved

Date submitted

29/01/2018

Date registered

5/02/2018

Date last updated

27/04/2023

Date data sharing statement initially provided

11/12/2018

Date results provided

27/04/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Influence of Non-Anaemic Iron Deficiency on Outcomes Following Cardiac Surgery

Scientific title

A prospective, observational study to determine if non-anaemic iron deficiency increases hospital stay and decreases days alive and at home in patients undergoing elective cardiac surgery.

Secondary ID [1]

HREC/Austin/16/308

Universal Trial Number (UTN)

U1111-1208-6520

Trial acronym

IDOCS

Linked study record

Not applicable

Health condition

Health condition(s) or problem(s) studied:

Iron deficiency

Cardiac surgical patients

Perioperative optimisation of elective surgery patients

Condition category

Condition code

Blood

Other blood disorders

Cardiovascular

Coronary heart disease

Anaesthesiology

Other anaesthesiology

Cardiovascular

Other cardiovascular diseases

Surgery

Other surgery

Metabolic and Endocrine

Other metabolic disorders

Diet and Nutrition

Other diet and nutrition disorders

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Elective cardiac surgical patients with non-anaemic iron deficiency at time of surgical booking.

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Elective cardiac surgical patients classified as non-anaemic, iron replete at time of surgical booking, with observation up to 90 days postoperatively.

Control group

Active

Outcomes

Primary outcome [1]

Days alive and out of hospital at post-operative day 30, assessed by data linkage to the medical record and study specific questionnaire.

Timepoint [1]

30 days following induction of anaesthesia for primary surgical procedure.

Secondary outcome [1]

Total number of days spent in ICU during the initial inpatient stay, assessed by data linkage to the medical record and study specific questionnaire.

Timepoint [1]

Initial inpatient stay hospital discharge.

Secondary outcome [2]

Total length of acute hospital stay during study, assessed by data linkage to the medical record and study specific questionnaire.

Timepoint [2]

90 days after induction of anaesthesia for the primary surgical procedure.

Secondary outcome [3]

Functional status as measured by EQ-5D-5L.

Timepoint [3]

Baseline and post-operative day 30.

Secondary outcome [4]

Disability status as measured by WHODAS 2.0.

Timepoint [4]

Baseline and post-operative day 90.

Secondary outcome [5]

Post-operative recovery as measured by QoR-15.

Timepoint [5]

Post-operative day 3.

Secondary outcome [6]

Mortality.

Timepoint [6]

90 days following induction of anaesthesia for the primary surgical procedure.

Secondary outcome [7]

Units of allogeneic blood transfused, as assessed by data linkage to the medical record.

Timepoint [7]

30 days following induction of anaesthesia for the primary surgical procedure.

Secondary outcome [8]

Surgical site infection rate, defined by the Centers for Disease Control and Prevention (CDC) with the National Healthcare safety Network (NHSN) criteria, and assessed using data linkage to the medical record.

Timepoint [8]

30 days following induction of anaesthesia for index procedure.

Secondary outcome [9]

Days alive and out of hospital at post-operative day 90 as assessed by data linkage to the medical record and study specific questionnaire.

Timepoint [9]

90 days following induction of anaesthesia for the primary surgical procedure.

Eligibility

Key inclusion criteria

Patients scheduled to undergo elective cardiac surgery.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Emergency or inpatient surgery.
Pregnancy.
Age < 18 years.
Known or suspected haemoglobinopathy.
Bone marrow disease.
Haemochromatosis.
End stage renal failure requiring dialysis.
Erythropoetin or iron (IV or oral) in the preceding 4 weeks prior to enrolment.

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Case control

Timing

Prospective

Statistical methods / analysis

SAMPLE SIZE

Sample size was calculated using data from a pilot study performed by our group (Miles LF, et al. Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and iron-deficient patients - an exploratory study. Anaesthesia, 2017; Epub ahead of print).
The primary endpoint (DAOH) has a left-skewed distribution with a spike at 0, mainly due to deaths in hospital post-surgery. Power was obtained by simulations (B = 20,000). DAOH-looking data were generated by simulating first length of stay (LOS) using a lognormal distribution, truncating it at 28 days (a plausible maximum based on existing data) and finally computing DAOH as 28 minus LOS. Such data are bimodal with a spike at 0 as required. The lognormal distribution was calibrated to generate DAOH with a median of 23 days and 5% zeroes in the control arm. A sample size of n = 480 (240/arm) has respectively 83% power to detect a median increase of 1.25 days using the Wilcoxon sum rank test for the analysis.

STATISTICAL ANALYSIS OF STUDY DATA

Continuous baseline variables will be analysed using Student’s T-test or Wilcoxon rank-sum test depending on normality. The chi-squared test or Fisher's exact test will be used for categorical endpoints.

The primary outcome measure, DAOH-30, will be modelled using median or, more generally, quantile regression. As DAOH-30 is left skewed with a spike at zero, it is more relevant to model the median (or alternatively, the 75th percentile) that is closer to the major distribution mode and directly interpretable. Difference in median DAOH between the two groups (patients with iron deficiency versus those who are iron replete) will be adjusted for potential known confounders (e.g. age, sex, haemoglobin, eGFR, etc.). A propensity score analysis will also be carried out.

A similar strategy will be used for DAOH-90 to assess whether findings are consistent over time. Binary outcomes will be analysed using logistic regression. Results will be expressed as odds ratios and 95% CI. Quality of life (QoL) scores like QoR-15 and EQ-5D-5L at 30 days will be treated like continuous outcomes and analysed using linear regression adjusted for the baseline reading. A repeated measures analysis based on mixed linear models will also be conducted to include QoL at 90 days. Time-to-event (disability free survival) will be analysed using Cox proportional hazard regression. Similar adjustment to the primary outcome will be carried out for all secondary endpoints. Safety endpoints will be tabulated and compared using exact logistic regression as number are like to be small and ideally we would like to adjust for potential confounders (non-randomised comparison).

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

22/02/2018

Actual

22/02/2018

Date of last participant enrolment

Anticipated

10/02/2020

Actual

11/02/2021

Date of last data collection

Anticipated

11/05/2020

Actual

8/05/2021

Sample size

Target

480

Accrual to date

Final

480

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

The Alfred - Prahran

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3004 - Prahran

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

ANZCA Research Foundation

Address [1]

PO Box 6095
Melbourne VIC 3004

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Health

Address

145 Studley Road
HEIDELBERG VIC 3084

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Not applicable

Address [1]

Not applicable

Country [1]

Other collaborator category [1]

University

Name [1]

Anaesthesia, Perioperative and Pain Medicine Unit, University of Melbourne

Address [1]

C/O Melbourne Medical School
The University of Melbourne
Grattan Street
PARKVILLE VIC 3010

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

Office for Research
Level 8, Lance Townsend Building
145 Studley Road
HEIDELBERG VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/08/2016

Approval date [1]

06/10/2016

Ethics approval number [1]

HREC/Austin/16/308

Summary

Brief summary

Adequate iron stores are essential for the ability of the body to produce new red blood cells, and the key component of those red blood cells, haemoglobin.  A low blood concentration of haemoglobin is referred to as “anaemia”, and is often due to low iron stores, or an inability for the bone marrow to access them.  This latter phenomenon is referred to as “iron deficiency”.  Iron deficiency and anaemic may exist in a patient separately, or together.  A combination of the two is termed “iron deficiency anaemia”, and patients with the condition are said to be “anaemic”.

Iron deficiency anaemia has long been associated with worse outcomes for patients undergoing cardiac surgery.  Compared to a normal person, the patient with iron deficiency anaemia has a higher risk of requiring a blood   transfusion, sustaining a kidney injury, or dying following their operation.  

There is another group that, up until now, has been poorly studied: those patients who are iron deficient, but not anaemic.  Whilst these patients may have a normal haemoglobin concentration in their blood prior to surgery, inevitable blood loss during surgery and the inflammation during and afterwards causes the haemoglobin concentration to fall.  If the patient has inadequate stores of iron, or is unable to access those stores, these patients will be unable to increase their production of haemoglobin.  Hypothetically, these patients are at risk of many of the complications that patients with anaemia prior to their operation will face. However, because this research question is yet to be formally studied, it is not known whether or not this is correct. 

Proposed trial and investigators

The IDOCS study has been designed to test this theory.  Patients with iron deficiency, but who are not anaemic before their operation will be followed during and after their surgery and compared to a cohort of normal patients (who are iron replete and not anaemic) as a reference point. If the trial hypothesis is correct, patients who are iron deficient but not anaemic will have worse outcomes than those patients who are not anaemic and iron replete.  

IDOCS will be undertaken at two major tertiary hospitals in Melbourne: The Alfred and the Austin Hospital.
 

Significance

If the hypothesis of IDOCS is proven, it will identify a new group of patients who are at risk of poor outcomes following cardiac surgery, opens an exciting new frontier in preparing patients for these procedures, and improving survival and reducing complications from the operation.

Trial website

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/374387-IDOCS Ethics Approval.rtf (Ethics approval)

Contacts

Principal investigator

Name

Dr Lachlan Miles

Address

Department of Anaesthesia, Austin Health
Level 2, Austin Tower
HEIDELBERG VIC 3084

Country

Australia

Phone

+61394965704

Fax

+61394596421

Lachlan.MILES@austin.org.au

Contact person for public queries

Name

Sarah Baulch

Address

Department of Anaesthesia, Austin Health
Level 2, Austin Tower
HEIDELBERG VIC 3084

Country

Australia

Phone

+61394965704

Fax

+61394596421

Sarah.BAULCH@austin.org.au

Contact person for scientific queries

Name

Lachlan Miles

Address

Department of Anaesthesia, Austin Health
Level 2, Austin Tower
HEIDELBERG VIC 3084

Country

Australia

Phone

+61394965704

Fax

+61394596421

Lachlan.MILES@austin.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified data relating to participant demographics and outcomes. No data that may be used to re-identify participants will be shared.

When will data be available (start and end dates)?

Data will be available after the publication of the primary manuscript resulting from the study (anticipated Dec. 2021). End date of IPD availability will be 7 years after the study concludes.

Available to whom?

Academic authors. Requests from industry unaffiliated with an academic body such as a University will not be considered.

Available for what types of analyses?

Meta-analysis and systematic review.

How or where can data be obtained?

Electronic transfer.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A protocol for prospective observational study to determine if non-anaemic iron deficiency worsens postoperative outcome in adult patients undergoing elective cardiac surgery: the IDOCS study.	2022	https://dx.doi.org/10.1186/s13741-022-00239-2
Embase	Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study.	2022	https://dx.doi.org/10.1016/S2352-3026%2822%2900142-9

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically