Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000653864
Ethics application status
Not yet submitted
Date submitted
7/06/2012
Date registered
19/06/2012
Date last updated
21/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety of RAPid INJECTion of Undiluted Ferric Carboxymaltose to Patients with Iron Deficiency Anaemia (RAPINJECT)
Scientific title
Safety of RAPid INJECTion of Undiluted Ferric Carboxymaltose to Patients with Iron Deficiency Anaemia (RAPINJECT): A phase II study
Secondary ID [1] 280566 0
Nil
Universal Trial Number (UTN)
Trial acronym
RAPINJECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Iron deficiency anaemia 286570 0
Condition category
Condition code
Blood 286844 286844 0 0
Anaemia
Diet and Nutrition 286947 286947 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A three stage study will be undertaken. Patients will be recruited to each stage in order of recruitment. Thus, the first 30 patients recruited will receive Stage 1 of the trial, the following 12 will receive Stage 2, and the final 100 will receive Stage 3. An additional 12 patients will be recruited to Stage 3 to account for potential loss to follow up.

Stage 1: Ferric carboxymaltose administered intravenously at a dose of up to 1000mg diluted in Normal Saline, administered over 15 minutes, as currently approved by the Therapeutic Goods Administration.

Stage 2: Ferric carboxymaltose administered intravenously undiluted, in a bolus over 1 minute, at escalating doses in successive patients: 400mg (3 patients), 600mg (3 patients), 800mg (3 patients) and 1000mg (6 patients).

Stage 3: Ferric carboxymaltose, administered intravenousl;y undiluted, in a bolus over 1 minute, at a dose of up to 1000mg as per patient requirements.

All doses will be administered once in the study.
Intervention code [1] 284952 0
Treatment: Drugs
Comparator / control treatment
All 3 stages of the study will be assessed with the same weight such that no one stage is classified as a control. Results from each stage will not be formally compared with each other.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287198 0
Infusion-related safety of rapid dose undiluted intravenous injection of FCM administered over 1 minute.

Measured by patient questioning, vital sign observations, clinical examination and ECG testing.
Timepoint [1] 287198 0
Immediately following infusion.
Secondary outcome [1] 297608 0
Overall (early and delayed) safety of rapid dose intravenous injection of FCM administered over 1 minute.

Measured by patient questioning, vital sign observations, clinical examination and ECG testing.
Timepoint [1] 297608 0
Immediately and up to 1 month following infusion.
Secondary outcome [2] 297609 0
Acceptability by patients of intravenous injection of FCM administered over 1 minute.
Timepoint [2] 297609 0
Immediately and up to 1 month following infusion.

Measured by patient questioning: patients will be asked whether they have would accept this treatment again in the future.
Secondary outcome [3] 297610 0
Efficacy of FCM administered over 1 minute in improving iron stores and haemoglobin concentration

Haemoglobin and iron stores (ferritin, transferrin saturation, serum iron) will be measured using patient samples collected at 2 weeks and 1 month from patients, and tested on laboratory analysers.
Timepoint [3] 297610 0
2 weeks and 1 month following infusion.

Eligibility
Key inclusion criteria
Patients with iron deficiency anaemia (defined as haemoglobin<120g/L in women, <130g/L in men; and either ferritin<100ng/mL or transferrin saturation<20%).

Clinical assessment by referring physician that intravenous iron replacement is required.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (for Stage 1):
Unwilling or unable to answer questions on adverse events.

Unwilling to participate in evaluation.

Patient or physician preference for IV iron product other than Ferric Carboxymaltose (this may be expected to occur in patients requiring total dose infusions exceeding 1000mg).

Exclusion Criteria (for Stage 2 and 3):
Patients currently admitted to an inpatient bed who are considered by the trial or treating physician to be unlikely to be discharged within the next two weeks,

Patients with severe anaemia requiring transfusion, defined as either requirement for transfusion based on clinician judgment or a haemoglobin concentration below 60g/L,

Patients with ongoing blood loss requiring urgent surgical or endoscopic intervention within the next 7 days (according to clinician judgment) - such patients would be eligible for the study following completion of the surgical procedure as long as other exclusion criteria were not fulfilled,

Patients with anaemia due to causes other than iron deficiency,

Patients with end stage renal failure requiring erythropoietin therapy,

Patients with another acute or chronic medical condition that in the opinion of the investigators, makes them an unsuitable candidate for enrolment in the study

Patients considered unwilling or unlikely to comply with the study or procedures,

Pregnant women (pre-menopausal women will be screened by serum B-HCG),

Patients with expected survival less than 3 months,

Patients with known hypersensitivity to intravenous iron formulations,

Patients with a recent (previous 4 weeks) history of atopy (asthma, urticaria or eczema),

Patients who have recently received (within the previous 4 weeks), expected to receive (within the next 4 weeks) or currently receiving erythropoietin therapy,

Patients with hereditary or transfusion acquired iron overload,

Patients with elevation of serum liver transaminases more than twice normal,

History of chronic abuse of analgesics, alcohol, tranquilizers, opioids or known drug

Dependence on alcohol or illicit drugs,

Treatment in the previous three months with any drug known to have a well-defined potential for toxicity to a major organ

Patients who have received an iron infusion within the previous 4 weeks.

Patients who have received a blood transfusion within the previous 2 weeks.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Referral
Patients will be referred by their treating physicians to the study investigator for consideration for enrolment. Referring practitioners will be informed about the study by letter and email as well as verbal communication to practitioners (i.e. gastroenterologists, obstetricians, anaesthetists and physicians and others) who frequently refer patients for intravenous iron infusions. Direct promotion of the study to patients will not occur.

Screening visit
Referred patients will be asked to attend for a screening visit. At this visit, patients will be informed about the study and their eligibility for participations will be ascertained according to the inclusion and exclusion criteria. If the patient is eligible and consents to enrolment, written informed consent will be obtained from a study medical practitioner. A blood sample will be taken for baseline blood tests.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Three stage study. Patients will be enrolled into each stage according to their order of recruitment. The first 30 patients will be enrolled into Stage 1, the next 12 will be enrolled into Stage 2, and the final 100 will be enrolled into Stage 3.
Stage 1, 30 patients will be administered iron carboxymaltose as per the TGA approved approach (up to 1000mg diluted in saline and administered over 15 minutes).
Stage 2, 12 patients will be assigned to a dose escalation study to identify any dose limiting toxicities associated with rapid infusion.
Stage 3, 100 subjects will be administered a total dose (based on calculated iron deficit up to 1000mg, maximum dose of 20mg/kg) of ferric carboxymaltose. An additional 12 patients will be recruited to this stage to account for potential loss to follow up/ incomplete data.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
154
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285331 0
Commercial sector/Industry
Name [1] 285331 0
Vifor Pharma Unrestricted Research Grant
Country [1] 285331 0
Switzerland
Primary sponsor type
Hospital
Name
Haematology Unit, Monash Medical Centre, Southern Health
Address
246 Clayton Road
Clayton 3168 VIC
Country
Australia
Secondary sponsor category [1] 284184 0
None
Name [1] 284184 0
N/A
Address [1] 284184 0
N/A
Country [1] 284184 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 287419 0
Ethics committee address [1] 287419 0
Ethics committee country [1] 287419 0
Date submitted for ethics approval [1] 287419 0
23/05/2012
Approval date [1] 287419 0
Ethics approval number [1] 287419 0

Summary
Brief summary
Iron deficiency anaemia remains an important clinical problem. Although oral iron is usually an adequate treatment, intravenous iron is often indicated. However, currently available agents available for total dose intravenous iron replacement require prolonged administration with admission to day wards or hospital beds, consuming considerable staff and patient time and health care resources. Ferric carboxymaltose, a novel iron-carbohydrate, has been extensively trialed and has been approved by the TGA for administration of up to 1000mg of iron (diluted in saline) intravenously over 15 minutes. This promises to greatly accelerate the treatment of iron deficiency anaemia. However, preliminary data suggest that high doses of undiluted ferric carboxymaltose may be safely administered even more quickly, by rapid bolus injection. Such an approach could revolutionize the treatment of iron deficiency as patients could receive total dose iron replacement in the clinic, without requiring a hospital bed or pharmacy. We propose a three stage, single arm study two determine the safety of rapid infusion of ferric carboxymaltose at doses of up to 1000mg. We plan to recruit patients with iron deficiency anaemia presenting to Southern Health into this three stage study. In Stage 1, 30 patients will be administered iron carboxymaltose as per the TGA approved approach (up to 1000mg diluted in saline and administered over 15 minutes). Subsequently, in Stage 2, 12 patients will be assigned to a dose escalation study to identify any dose limiting toxicities associated with rapid infusion. Finally, in Stage 3, 100 subjects will be administered a total dose (based on calculated iron deficit up to 1000mg, maximum dose of 20mg/kg) of ferric carboxymaltose. The primary outcome of the study is the incidence of adverse events related to rapid infusion.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 34234 0
Address 34234 0
Country 34234 0
Phone 34234 0
Fax 34234 0
Email 34234 0
Contact person for public queries
Name 17481 0
Dr Sanjeev Chunilal
Address 17481 0
Haematology Unit,
Monash Medical Centre,
246 Clayton Road, Clayon Victoria 3168
Country 17481 0
Australia
Phone 17481 0
+61 3 9594 4366
Fax 17481 0
+61 3 9594 6587
Email 17481 0
[email protected]
Contact person for scientific queries
Name 8409 0
Dr Sanjeev Chunilal
Address 8409 0
Haematology Unit,
Monash Medical Centre,
246 Clayton Road, Clayon Victoria 3168
Country 8409 0
Australia
Phone 8409 0
+61 3 9594 4366
Fax 8409 0
+61 3 9594 6587
Email 8409 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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