Clinical Trial Results:
Is intravenous iron and darbepoetin more effective than oral iron in reducing blood transfusion requirements for patients undergoing cardiac surgery
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Summary
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EudraCT number |
2011-003695-36 |
Trial protocol |
GB |
Global end of trial date |
11 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jan 2020
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First version publication date |
31 Jan 2020
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Other versions |
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Summary report(s) |
INITIATE Clinical study summary report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
11/LO/1310
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Additional study identifiers
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ISRCTN number |
ISRCTN41421863 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Brighton and Sussex University Hospitals Trust
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Sponsor organisation address |
Royal Sussex County Hospital Eastern Road, Brighton, United Kingdom, BN2 5BE
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Public contact |
Mr Scott Harfield, Brighton and Sussex University Hospitals, 044 01273 696955, Scott.Harfield@bsuh.nhs.uk
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Scientific contact |
Mr Scott Harfield, Brighton and Sussex University Hospitals, 044 01273 696955, Scott.Harfield@bsuh.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Nov 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Nov 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Nov 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
In patients who have a low haemoglobin level before surgery, will treatment using a combination of intravenous iron and darbepoetin result in less blood transfusion after heart surgery than treatment using iron tablets alone.
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Protection of trial subjects |
Patients were given full advice and information through the participation information sheet before being
asked if they wished to participate in the study and once involved they were asked at each visit whether
they wished to continue and were free to withdraw from the study. After treatment the patients were
monitored to ensure they were in no distress and all was well before being told that they were free to
return home. They were given the contact numbers of the research staff in case they had any queries
and also the contact details of the Patient Advice and Liaison Service
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 170
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Worldwide total number of subjects |
170
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EEA total number of subjects |
170
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
170
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Intervention group analysed: 79 Standard care group analysed: 77 Total randomised: 170 | |||||||||||||||
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Pre-assignment
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Screening details |
2799 patients undergoing elective cardiac surgery at the centre were screened for eligibility. An Hb concentration between 100 and 130 g/L (inclusive) was required for inclusion | |||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention | |||||||||||||||
Arm description |
Participants in the intervention group received a total dose infusion of iron (III) isomaltoside 1000 (Monofer®). The dose of 1000mg (or 20mg/kg if body weight less than 50kg) was infused | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
iron (III) isomaltoside 1000 (Monofer®).
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Participants in the intervention group received a total dose infusion of iron (III) isomaltoside 1000 (Monofer®). The dose of 1000mg (or 20mg/kg if body weight less than 50kg) was infused according to the manufacturer’s recommended protocol via a peripheral vein
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Arm title
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Standard of care | |||||||||||||||
Arm description |
Participants randomised to Standard Care were instructed to see their GP as soon as possible. The participant was given a prescription for 2 week supply of ferrous sulphate and prescribed the maximum tolerated dose of oral ferrous sulphate (starting at 200mg x 3 per day) until the day of surgery. Participants who do not tolerate this dose will be asked to reduce the dose to 200mg x2 or 200mg x1 per day. Concurrent deficiencies in vitamin B12 or folate or abnormal thyroid function will be treated according to standard practice. | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
ferrous sulphate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants randomised to Standard Care were instructed to see their GP as soon as possible. The participant was given a prescription for 2 week supply of ferrous sulphate and prescribed the maximum tolerated dose of oral ferrous sulphate (starting at 200mg x 3 per day) until the day of surgery. Participants who do not tolerate this dose will be asked to reduce the dose to 200mg x2 or 200mg x1 per day. Concurrent deficiencies in vitamin B12 or folate or abnormal thyroid function will be treated according to standard practice.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Participants in the intervention group received a total dose infusion of iron (III) isomaltoside 1000 (Monofer®). The dose of 1000mg (or 20mg/kg if body weight less than 50kg) was infused | ||
Reporting group title |
Standard of care
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Reporting group description |
Participants randomised to Standard Care were instructed to see their GP as soon as possible. The participant was given a prescription for 2 week supply of ferrous sulphate and prescribed the maximum tolerated dose of oral ferrous sulphate (starting at 200mg x 3 per day) until the day of surgery. Participants who do not tolerate this dose will be asked to reduce the dose to 200mg x2 or 200mg x1 per day. Concurrent deficiencies in vitamin B12 or folate or abnormal thyroid function will be treated according to standard practice. | ||
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End point title |
Did participant receive one red cell transfusion on days 0-5 [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0-5 days post surgery
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See attached documents for results |
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Attachments |
INITIATE Analysis |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
For the duration of the study
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
18
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: See attached documents for adverse events |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Mar 2013 |
Addition to, and clarification of, the exclusion criteria and stipulation of SAE reporting process |
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06 Sep 2013 |
1. Clarification that a change in Hb count prior to randomisation will not necessarily result in the participant becoming ineligible for the study.
2. Indicating that the intravenous iron infusions may be done in CIRU.
3. Clarifying that the end of study visit may not necessarily be 6-weeks after surgery, but whenever the post-operative outpatient appointment takes place.
4. Amending the AE and SAE reporting to suggest that all AEs will only require recording for trial purposes between IMP administration and surgery, and not post-surgery. SAEs and recognised complications during and after surgery should not be recorded if listed as expected in table 14.3.
5. Updating Hb measurement to the new guidelines (g/l instead of g/dl) |
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29 Sep 2016 |
Allowance for interim analysis |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
