Clinical Trial Results:
Efficacy and safety of ANAkinra during Adult « COVID-19 » with Aggravating respiratory symptoms: a multicenter open-label controlled randomized trial
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Summary
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EudraCT number |
2020-001734-36 |
Trial protocol |
FR |
Global end of trial date |
03 Nov 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
27 May 2022
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First version publication date |
27 May 2022
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Other versions |
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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 |
DR200111
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04364009 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CHRU Tours
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Sponsor organisation address |
Boulevard Tonnellé, Tours, France, 37044 cedex 9
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Public contact |
Clinical Research Associate, CHRU de TOURS, +33 247474665, e.mousset@chu-tours.fr
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Scientific contact |
Coordinating investigator, CHRU de TOURS, +33 247473715, alexandra.audemardverger@univ-tours.fr
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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 |
03 Nov 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of the ANACONDA-COVID-19 trial is to assess the efficacy of Anakinra + optimized Standard of Care (oSOC) as compared to oSOC alone on the condition of patients with COVID-19 infection and worsening respiratory symptoms. Success defined as patient alive and free of invasive mechanical ventilation (IMV) and free of Extracorporeal Membrane Oxygenation (ECMO) at Day 14.
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Protection of trial subjects |
An interim analysis for efficacy analysis was planned after the primary outcome has been obtained for the first 120 patients and for safety concerns each 60 patients.
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Background therapy |
- | ||
Evidence for comparator |
Analgesic treatment, transfusion of blood products, electrolyte and glucose infusions, IV, parenteral nutrition, inotropic support, antibiotics, anti-fungal and anti-viral treatments, ultrafiltration or hemodialysis, as well as general supportive care were allowed. Other therapy considered necessary for the patient’s welfare could be given at the discretion of the Investigator. Due to the lack of sufficient scientific evidence hydroxychloroquine chloroquine and antiretrovirals were not recommended but not prohibited because clinical trials were ongoing. Regarding corticosteroid therapy, due to a potential effectiveness, and the absence of a clearly negative study and a potential synergy with Anakinra, the clinician taking the choice of whether or not to initiate corticosteroid therapy support the patient. A standardized corticosteroid regimen was proposed. Randomization was stratified on the presence or absence of corticosteroid therapy and don’t lead to bias in our study | ||
Actual start date of recruitment |
27 Apr 2020
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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 |
France: 71
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Worldwide total number of subjects |
71
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EEA total number of subjects |
71
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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) |
20
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From 65 to 84 years |
41
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85 years and over |
10
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Recruitment
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Recruitment details |
The recruitment started on 27th avril 2020. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Patients were screened by 45 COVID referent centers. All patients with a positive COVID-19 diagnosis were considered for inclusions. Inclusion and exclusion criteria were first checked during a routine/daily medical visit. The duration of screening period should not exceed 24h. | ||||||||||||||||||
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Period 1
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Period 1 title |
Inclusion
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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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Anakinra plus optimized standard of care | ||||||||||||||||||
Arm description |
The experimental group received Anakinra plus optimized standard of care. The patients received intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Kineret
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The patients received Intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) during 3 days. Then, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours) during 7 days. The total duration of Anakinra is 10 Days.
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Arm title
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optimized standard of care | ||||||||||||||||||
Arm description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||||||||||||||||||
Arm type |
Usual care | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 2
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Period 2 title |
Day 14
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
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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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Anakinra+SOC | ||||||||||||||||||
Arm description |
The experimental group received Anakinra plus optimized Standard of Care. The patients received Intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Kineret
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The patients received Intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) during 3 days. Then, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours) during 7 days. The total duration of Anakinra is 10 Days.
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Arm title
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Optimized Standard of Care | ||||||||||||||||||
Arm description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||||||||||||||||||
Arm type |
Usual care | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Anakinra plus optimized standard of care
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Reporting group description |
The experimental group received Anakinra plus optimized standard of care. The patients received intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
optimized standard of care
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Reporting group description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Anakinra plus optimized standard of care
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Reporting group description |
The experimental group received Anakinra plus optimized standard of care. The patients received intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days. | ||
Reporting group title |
optimized standard of care
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Reporting group description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||
Reporting group title |
Anakinra+SOC
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Reporting group description |
The experimental group received Anakinra plus optimized Standard of Care. The patients received Intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days | ||
Reporting group title |
Optimized Standard of Care
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Reporting group description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||
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End point title |
Treatment success at day 14 | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At day 14
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Attachments |
Untitled (Filename: Flow_chart.jpg) |
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Statistical analysis title |
Risk difference | |||||||||
Comparison groups |
optimized standard of care v Anakinra plus optimized standard of care
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Number of subjects included in analysis |
71
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
-20.9
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-39.2 | |||||||||
upper limit |
-1.8 | |||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Real time reporting from the day that written informed consent is provided until 28 days after the inclusion
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Adverse event reporting additional description |
This initial reporting must be provided in writing and should quickly be followed by a detailed written supplementary report
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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 |
23.1
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Reporting groups
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Reporting group title |
Anakinra plus optimized standard of care
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Reporting group description |
The experimental group received Anakinra plus optimized Standard of Care. The patients received Intraveinous injection (IV) of Anakinra 400mg/day (100mg IV every 6 hours) at Day 1, 2 and 3. From Day 4 to Day 10, the patient received IV injection of Anakinra 200mg/day (100mg every 12 hours). The total duration of Anakinra was 10 Days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
optimized standard of care
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Reporting group description |
The control group received optimized standard of care alone, including all treatments authorized for COVID-19 by the French Health Ministry at inclusion and during the follow-up. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: The list of adverse events is not available. |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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11 May 2020 |
- Addition of 4 centers
- Protocole's modification : At V3, for the group SOC alone, this visit will be performed at hospital or by phone if the patient is discharged from the hospital in order to avoid hospital saturation |
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25 May 2020 |
- Restart of inclusions after the declaration of a new-fact
- Modification of DSMB meeting
- Addition of 4 centers |
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18 Jun 2020 |
- Prolongation of period recruitment |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 | |||||||
