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Trial registered on ANZCTR


Registration number
ACTRN12614001261606
Ethics application status
Approved
Date submitted
20/11/2014
Date registered
3/12/2014
Date last updated
21/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of a single intravenous iron infusion versus standard care in the management of Post-OPerative Iron (POPi) deficiency anaemia patients undergoing elective surgery at the Launceston General Hospital
Scientific title
Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: A prospective randomised controlled trial
Secondary ID [1] 285707 0
None
Universal Trial Number (UTN)
Trial acronym
Post-OPerative Iron deficiency anaemia trial (POPi)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
post-operative iron deficiency anaemia 293577 0
Condition category
Condition code
Blood 293860 293860 0 0
Anaemia
Surgery 293921 293921 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with post-operative anaemia will be randomised between standard care after surgery and a single iron carboxymaltose infusion 15mg/Kg body weight once only infused over 15 minutes within 24-48 hours post-operatively.

Intervention code [1] 290655 0
Treatment: Drugs
Comparator / control treatment
1. Age and sex matched postoperative patients with normal iron stores/Hb postoperatively who receive routine postoperative care after their consent.
2. Patients with post-operative anaemia allocated to the control group receive standard care, which is defined as management of postoperative anaemia with blood transfusion according to hospital guidelines.
Control group
Active

Outcomes
Primary outcome [1] 293640 0
To assess the efficacy of IV iron in postoperative anaemia setting

Tools: Via full blood count with measurement of Haemoglobin (Hb) and assay of serum iron studies measurement
Timepoint [1] 293640 0
this timepoint will be measured at discharge, 4 weeks and at the end of the study at 3 months.
Primary outcome [2] 293641 0
To assess blood transfusion requirement in both groups of patients.
Timepoint [2] 293641 0
Number of transfused blood units /Amount of blood until discharge
Primary outcome [3] 293642 0
To assess the prevalence of postoperative iron deficiency anaemia among patients who present to the LGH for elective surgery by recording all anaemic patients versus total number of surgery on the specified trial period.
Timepoint [3] 293642 0
until the end of study approx 18 months
Secondary outcome [1] 311508 0
To assess drug safety, and tolerability by a specially designed tolerability assessment form conducted by the treating medical staff during the admission .
Timepoint [1] 311508 0
until patient discharge
Secondary outcome [2] 311509 0
patient outcome in termms of recovery postoperatively.

Parameters to be assessed via Postoperative Recovery Profile (PRP), alive status and overall performance at discharge.
Timepoint [2] 311509 0
by patients discharge.
Secondary outcome [3] 311510 0
To assess effect on quality of life with SF-36 Quality of Life Questionnaire
Timepoint [3] 311510 0
By discharge from hospital, 4weeks and 12 weeks postoperatively.
Secondary outcome [4] 311511 0
To assess post-operative complications in relation to anaemia such as anaemia symptoms requirement for blood transfusion, infection.

This will be done through hospital notes and radiology and laboratory and diagnostics
Timepoint [4] 311511 0
by discharge until end of study at 3 months.
Secondary outcome [5] 311688 0
Lenghth of hospital stay (LOS)
Timepoint [5] 311688 0
Number of days of hospital admission from the operative procedure date till patients discharge date.

Eligibility
Key inclusion criteria
The inclusion criteria for anaemic patients who undergoing elective surgery in the study will be a haemoglobin level equal or above 70 g/L, but < 120 g/L as measured by an accredited LGH pathology laboratory in addition to low iron stores and or low iron saturation equal or <20%.
Patients who undergoing elective surgery with Hb >120 g/L will serve as control group.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of a specific cause for anaemia apart from haematinic deficiency
Patients with active infection and or sepsis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This study is to assess the effect of intravenous single iron therapy versus standard care for patients after surgery in the Launceston General Hospital. Patients who receive the standard care and not eligible for the study will be also followed up to assess their outcomes with their consent. The study will be explained in detail to the patients mainly preoperatively, and if necessary postoperatively and a written informed consent will be obtained from all subjects prior to their enrolment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A full patient profile will be obtained including medical and drug history, usual diet and exercise regime. The patient’s demographic and physical detail (weight, height etc) will be measured and recorded.

Eligible patients for the trial will be counselled on any side effects from the iron and ensured that if they decide to withdraw from the study at any time this will in no way affect their care or procedure at the LGH.

The patients will be randomized by an impartial party in the Pharmacy Department to avoid any possible bias using a randomly assigned computed system. The research assistant at enrolment will use the random assigned number schedule issued by the pharmacy. Patients will be randomized initially to 1) intravenous iron or 2) standard care.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary end points will be Hb, iron studies levels at discharge, amount of transfused blood, lenghth of stay at the hospital. The study design is a randomised controlled trial with two-way randomisation. Multivariable analyses will be conducted to compare the outcomes in the two treatment groups, unadjusted and adjusted for actual and potential confounding variables (e.g. age, gender, initial Hb, and operation site, body weight, final post-operative Hb where relevant): post-operative Hb and ferritin levels by repeated measures ANOVA using general linear modelling; peri-operative blood transfusion volumes by Poisson regression.

It is estimated that we would screen about 1000-2000 patients over an 18-24 month period, and that 10% of these would fit the inclusion criteria. Sample size calculations indicate a requirement for 52 completed patients per treatment group for both outcomes based on assumptions: i) a minimum effect size detection of 2g/l increase in postoperative Hb and a 45% reduction in units of blood transfused; ii) an untreated rise in Hb of 0g/l and SD 2.8g/l, and an expected untreated transfusion rate of 2.2 units per patient SD 1.8g/l (data from ‘Iron pre-load for major joint replacement’ Transfusion Medicine 1997; 7: 281-6); iii) alpha value of 0.05 and power of 80% allowing drop-out and missing data. A minimum effect size reduction of 36% in transfusion rate would require 100 patients per group (200 in total).





Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
TAS
Recruitment postcode(s) [1] 8967 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 290282 0
Hospital
Name [1] 290282 0
Launceston General Hospital
Address [1] 290282 0
Charles street
Launceston, Tasmania 7250
Australia
Country [1] 290282 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
Newnaham Drive
Launceston
Tasmania 7250
Country
Australia
Secondary sponsor category [1] 289027 0
Hospital
Name [1] 289027 0
Launceston General hospital
Address [1] 289027 0
Charles Street
Tasmania
7250
Country [1] 289027 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291983 0
Tasmanian Human Research Ethics Committee
Ethics committee address [1] 291983 0
University of Tasmania
Private Bag 01
Hobart, Tas 7001
Australia
Ethics committee country [1] 291983 0
Australia
Date submitted for ethics approval [1] 291983 0
Approval date [1] 291983 0
18/11/2014
Ethics approval number [1] 291983 0
H0014351

Summary
Brief summary
Since 2007, we have conducted several studies assessing preoperative anaemia in different settings including elective surgery. We noted that there was an inherent delay in the management of preoperative anaemia with most of these patients proceeding with the planned surgery without having their iron deficiency anaemia addressed. Despite the improvement in preoperative management, it has been found that there are a significant, although unknown number of patients who have postoperative iron deficiency anaemia. Furthermore, there is lack of data regarding prevalence of postoperative iron deficiency anaemia or amount of blood transfusions in patients who undergo elective surgery. Hence the importance of this trial to study all of these factors in Tasmanian patients attending the Launceston General Hospital in order to provide a pragmatic solution to this problem of postoperative anaemia.

This study is aiming to recruit patients with iron defciency anaemia and to then randomise them between administration of a single intravenous iron carboxymaltose and standard care.

Participants will be followed up by the research assistant from the time of recruitment/randomisation until 3 months post-operatively. This allows for the completion of a questionnaire regarding their wellbeing at the time, outcome of trial medications, and blood tests as required.

In summary, this study is dealing with an important problem, post-operative anaemia after surgery patients, an issue that to date has not been addressed by our health system, and which is usually significantly increased in this group of patients.

This trial is focusing on treating postoperative anaemia adequately to minimize risk factors of anaemia and to avoid blood transfusion and hence its subsequent complications/hazards. Another possible benefit of this trial is that it will help to relieve the current shortage of blood supply from the Red Cross. We also aim to minimize the patient’s stay in hospital and improve their quality of life.

Iron infusion would be performed in the LGH utilising the currently available facilities. The newly available iron infusion (15 min) is part of standard therapy and is routinely performed in this area without adding extra load to the system.
Trial website
Trial related presentations / publications
Alhossain Khalafallah, Vinod Khelgi, Raghad Al-Badri, Ella Robinson, Carl Yan, Jocelyn Tan, Rizwan Khan, Hung Nguyen and Brian Krikby
INTRAVENOUS IRON CARBOXYMALTOSE VERSUS STANDARD CARE IN THE MANAGEMENT OF POSTOPERATIVE ANAEMIA: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
(Abstract release date: May 21, 2015) EHA Learning Center. Khalafallah A. Jun 12, 2015; 100621 Label: Red blood cells and iron - Clinical 1

http://learningcenter.ehaweb.org/eha/2015/20th/100621/alhossain.khalafallah.intravenous.iron.carboxymaltose.
Public notes

Contacts
Principal investigator
Name 52942 0
Prof A/Professor Alhossain A. Khalafallah
Address 52942 0
Launceston General Hospital Charles Street, Launceston, TAS 7250
Country 52942 0
Australia
Phone 52942 0
+61373487111
Fax 52942 0
+61373487695
Email 52942 0
khalafallah@dhhs.tas.gov.au
Contact person for public queries
Name 52943 0
Prof A/Professor Alhossain A. Khalafallah
Address 52943 0
Launceston General Hospital Charles Street, Launceston, TAS 7250
Country 52943 0
Australia
Phone 52943 0
+61373487111
Fax 52943 0
+61373487695
Email 52943 0
khalafallah@dhhs.tas.gov.au
Contact person for scientific queries
Name 52944 0
Prof A/Professor Alhossain A. Khalafallah
Address 52944 0
Launceston General Hospital Charles Street, Launceston, TAS 7250
Country 52944 0
Australia
Phone 52944 0
+61373487111
Fax 52944 0
+61373487695
Email 52944 0
khalafallah@dhhs.tas.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary