Clinical Trial Results:
INtravenous Iron to Treat Anaemia in CriTical Care Survivors (INTACT): a feasibility study
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Summary
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EudraCT number |
2018-000767-91 |
Trial protocol |
GB |
Global end of trial date |
16 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
06 May 2021
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First version publication date |
06 May 2021
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Other versions |
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Summary report(s) |
Manuscript draft |
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 |
PID13493
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Additional study identifiers
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ISRCTN number |
ISRCTN13721808 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1209-6873 | ||
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Sponsors
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Sponsor organisation name |
University of Oxford
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Sponsor organisation address |
University Offices, Wellington Square, Oxford, United Kingdom, OX1 2JD
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Public contact |
Akshay Shah, University of Oxford, +44 1865387906, akshay.shah@ndcls.ox.ac.uk
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Scientific contact |
Akshay Shah, University of Oxford, +44 1865387906, akshay.shah@ndcls.ox.ac.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 |
04 Mar 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Mar 2020
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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 |
This is a feasibility study aiming to find out whether it is possible to give intravenous (through a drip) iron to patients with anaemia (low blood count) who have survived intensive care (ICU). A feasibility study is a short trial with a small number of people taking part, to help us decide how a larger study would work. Important questions that we are asking in this feasibility study are
(i) How easy is it to recruit participants?
(ii) How easy is it to collect the relevant information we would need for a future large trial?
Our ultimate aim is to complete a larger trial which will test whether or not intravenous iron will treat anaemia in ICU survivors and improve quality of life after discharge from hospital. This would require external funding and be a separate ethics application.
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Protection of trial subjects |
The trial had two committees:
(1) Trial Management Group (TMG)
The TMG will be responsible for the day to day running and management of the trial. A core team consisting of the CI and up to three other investigators will aim to meet at least two weekly during the planning stages of the trial and with the wider team less frequently when the trial is running.
(2) Trial Oversight Group (TOG)
The TOG will include independent clinicians experienced in the fields of clinical trials, intensive care and haematology along with an independent statistician. The TOG will work closely with the TMG and will provide overall supervision of the trial through its independent chair.
The TOG responsibilities will include:
- Provide overall supervision of the trial and to ensure it is being conducted in accordance with Good Clinical Practice
- Advise on protocol development and ensure adherence to the protocol during the trial period.
- Establish frequency of meetings prior to commencement of trial
- Provide advice to the CI and TMG through its independent chair and funding body, if appropriate, on all aspects of the trial
- Review AE and SAEs reported by the CI
- Monitor safety of study participants and to suggest any amendments to the protocol or termination of the trial if deemed necessary for patient safety
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2018
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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: 98
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Worldwide total number of subjects |
98
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EEA total number of subjects |
0
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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) |
50
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From 65 to 84 years |
46
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85 years and over |
2
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Recruitment
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Recruitment details |
Patients were enrolled from four ICUs across three centres (Oxford University Hospitals NHS Foundation Trust, Royal Infirmary of Edinburgh NHS Lothian, Royal Berkshire Hospital NHS Foundation Trust) from 17th September 2019 to 20th December 2020 with final patient follow-up completed on 13th March 2020. | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 606 patients were screened, and of the 290 (48%) that were eligible for recruitment, 98 (34%) were randomised over 15 months. | ||||||||||||||||||
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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 | ||||||||||||||||||
Blinding implementation details |
Open label study
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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 (Iv iron) arm | ||||||||||||||||||
Arm description |
Participants randomised to the IV iron group received, in addition to usual care, a single dose of 1000mg of ferric carboxymaltose diluted in 100mls of 0.9% saline as an infusion over 15 minutes. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Ferric carboxymaltose
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants randomised to the IV iron group received, in addition to usual care, a single dose of 1000mg of ferric
carboxymaltose diluted in 100mls of 0.9% saline as an infusion over 15 minutes.
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Arm title
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Comparator | ||||||||||||||||||
Arm description |
Usual medical care consisting of monitoring and red blood cell transfusion if required | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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End points reporting groups
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Reporting group title |
Intervention (Iv iron) arm
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Reporting group description |
Participants randomised to the IV iron group received, in addition to usual care, a single dose of 1000mg of ferric carboxymaltose diluted in 100mls of 0.9% saline as an infusion over 15 minutes. | ||
Reporting group title |
Comparator
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Reporting group description |
Usual medical care consisting of monitoring and red blood cell transfusion if required | ||
Subject analysis set title |
Primary feasibility outcomes
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Recruitment rate was calculated by the number of participants randomised as a proportion of the total number of eligible
patients. The protocol adherence rate was calculated as the number of participants allocated to the intervention who
received the study drug over the number of participants allocated to the intervention. HRQoL questionnaire completion
rates were calculated as the number completed at each time point over the number expected (total randomised less those
participants who died). Rates, together with 95% confidence intervals (CIs) were estimated based on data collected are
reported.
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Subject analysis set title |
Secondary outcomes
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Secondary outcomes included the following clinical, laboratory and HRQoL outcomes: (i) incidence of new nosocomial infection; (ii) in-hospital mortality; (iii) hospital LOS; (iv) changes in Hb, iron profiles, hepcidin and routine biochemistry from blood samples collected at baseline, 28 and 90 days post-randomisation; (v) HRQoL measured by Multidimensional Fatigue Inventory-20 (MFI-20), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and EuroQoL-5D-5L (EQ-5D-5L) questionnaires collected at baseline (pre-randomisation), and 28 and 90 days post-randomisation; and (vi) healthcare resource use, including hospital readmissions.
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End point title |
Recruitment rate | |||||||||
End point description |
Between September 2018 and December 2019, 290 (48%) of 606 patients approached were eligible to consent to participate. The overall recruitment rate for the trial was 34% (95% CI 28% to 40%). Overall, 98 patients were recruited from 3 sites over 15 months, a rate of 6.5 per month meeting the amber category for the stop-go criteria in the trial (Table 11).
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End point type |
Primary
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End point timeframe |
September 2018 to December 2019.
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Statistical analysis title |
Recruitment and randomisation rate | |||||||||
Statistical analysis description |
Recruitment rate was calculated by the number of participants randomised as a proportion of the total number of eligible
patients.
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Comparison groups |
Intervention (Iv iron) arm v Comparator
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Number of subjects included in analysis |
98
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
95% CI | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
28 | |||||||||
upper limit |
40 | |||||||||
| Notes [1] - Feasibility outcome |
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End point title |
Protocol adherence | |||||||||
End point description |
Of the 49 participants randomised to receive IV iron, 47 received it (96%, 95% CI 86% to 100%). One participant died and one participant withdrew before IV iron was administered.
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End point type |
Primary
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End point timeframe |
September 2018 to December 2019
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Statistical analysis title |
Protocol adherence | |||||||||
Statistical analysis description |
Of the 49 participants randomised to receive IV iron, 47 received it (96%, 95% CI 86% to 100%). One participant died and one participant withdrew before IV iron was administered.
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Comparison groups |
Intervention (Iv iron) arm v Comparator
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Number of subjects included in analysis |
96
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
95% Confidence interval | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
86 | |||||||||
upper limit |
100 | |||||||||
| Notes [2] - Feasibility outcome |
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End point title |
Follow-up rate | |||||||||
End point description |
All HRQoL outcomes were collected for at least 80% of survivors at 90 days.
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End point type |
Primary
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End point timeframe |
September 2018 to March 2020
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Statistical analysis title |
Follow-up rates | |||||||||
Statistical analysis description |
HRQoL questionnaire completion rates were calculated as the number completed at each time point over the number expected (total randomised less those participants who died).
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Comparison groups |
Intervention (Iv iron) arm v Comparator
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Number of subjects included in analysis |
98
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
95% Confidence interval | |||||||||
Confidence interval |
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| Notes [3] - Feasibility outcome |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Overall trial period
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Adverse event reporting additional description |
The following rare events, if serious, must be reported on the trial specific SAE form:
Anaphylactic/anaphylactoid reactions
Loss of consciousness / syncope
Bronchospasm
Angioedema and facial oedema
Severe anaemia (Hb <80 g.l-1) at 28 and/or 90-day post randomisation follow-up
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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 |
21
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Reporting groups
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Reporting group title |
Intervention (IV iron) group
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Reporting group description |
- | |||||||||||||||
Reporting group title |
Comparator (usual care) group
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Reporting group description |
- | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||
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| 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: No pre-defined SAEs or non-SAEs occurred during the course of the trial. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| Our trial has limitations. It was open label, which may have introduced performance bias, particularly for HRQoL measures, and attrition bias. Ferric carboxymaltose is a challenging and costly substance to blind due to its rusty brown colour. | |||
