Clinical Trial Results:
Phase 1 study of use of 5% Carbogen in treatment of paediatric non-convulsive status epilepticus
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Summary
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EudraCT number |
2011-005318-12 |
Trial protocol |
GB |
Global end of trial date |
12 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jul 2016
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First version publication date |
29 Jul 2016
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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 |
NCTU:CONCEPT1
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Additional study identifiers
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ISRCTN number |
ISRCTN80717736 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
EudraCT: 2011-005318-12, UKCRN ID: 12223 | ||
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Sponsors
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Sponsor organisation name |
The Newcastle upon Tyne Hospitals NHS Foundation Trust
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Sponsor organisation address |
Freeman Hospital, Freeman Road,, Newcastle upon Tyne, United Kingdom, NE7 7DN
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Public contact |
Dr Rob Forsyth, The Newcastle upon Tyne Hospitals NHS Foundation Trust, 44 191 256 3820, r.j.forsyth@newcastle.ac.uk
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Scientific contact |
Dr Rob Forsyth, The Newcastle upon Tyne Hospitals NHS Foundation Trust, 44 191 256 3820, r.j.forsyth@newcastle.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 |
07 Jul 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jan 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Jan 2015
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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 |
To assess the feasibility of the protocol and of data collection (blood gases, respiratory rate, breathlessness) and to confirm recruitment rates to inform the design of a definitive randomised controlled trial.
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Protection of trial subjects |
DMC suggested extension of EEG monitoring of participants post inhalation of IMP from 2 to 15 minutes and this was incorporated into substantial amendment 3 to the protocol.
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Background therapy |
Participants attended hospital with non-convulsive status epilepticus for control of seizure therefore there were no restrictions on concurrent medications to be used. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Mar 2013
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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: 6
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Worldwide total number of subjects |
6
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EEA total number of subjects |
6
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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) |
5
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
0
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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 |
The parents of eligible children known to the paediatric neurology services at site and deemed “at risk” of developing non-convulsive status epilepticus (NCSE) were notified, by letter, of the trial. Otherwise the parents of potentially eligible children were approached upon presentation at hospital. | ||||||||||
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Pre-assignment
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Screening details |
The trial was conducted in an emergency setting therefore screening was performed upon presentation of the child at hospital with suspected NSCE. Consent in principal was obtained from the child’s parent or guardian before EEG was performed to confirm presence of NCSE and confirmation of normal blood gas result. | ||||||||||
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Pre-assignment period milestones
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Number of subjects started |
6 | ||||||||||
Number of subjects completed |
6 | ||||||||||
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Period 1
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Period 1 title |
Preinhalation
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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5% Carbogen | ||||||||||
Arm description |
Inhalation of 5% Carbogen | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
5% carbon dioxide/oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, compressed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Administration of 5% carbogen by spontaneous inhalation administered via a loosely attached face mask (flow rate 15 litres/minute) for a period of 120 seconds.
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Period 2
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Period 2 title |
Immediately post-inhalation
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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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Arm title
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5% Carbogen | ||||||||||
Arm description |
Inhalation of 5% carbogen over a 120 second period | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
5% carbon dioxide/oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, compressed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Administration of 5% carbogen by spontaneous inhalation administered via a loosely attached face mask (flow rate 15 litres/minute) for a period of 120 seconds.
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Period 3
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Period 3 title |
24 hours post-inhalation
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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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Arm title
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5% Carbogen | ||||||||||
Arm description |
Inhalation of 5% Carbogen | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
5% carbon dioxide/oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, compressed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Administration of 5% carbogen by spontaneous inhalation administered via a loosely attached face mask (flow rate 15 litres/minute) for a period of 120 seconds.
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Period 4
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Period 4 title |
7 days post-inhalation
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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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Arm title
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5% Carbogen | ||||||||||
Arm description |
Inhalation of 5% Carbogen | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
5% carbon dioxide/oxygen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, compressed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Administration of 5% carbogen by spontaneous inhalation administered via a loosely attached face mask (flow rate 15 litres/minute) for a period of 120 seconds.
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Baseline characteristics reporting groups
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Reporting group title |
Preinhalation
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Reporting group description |
Inhalation of 5% carbogen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Carbogen Tolerability
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects that underwent treatment with carbogen.
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End points reporting groups
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Reporting group title |
5% Carbogen
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Reporting group description |
Inhalation of 5% Carbogen | ||
Reporting group title |
5% Carbogen
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Reporting group description |
Inhalation of 5% carbogen over a 120 second period | ||
Reporting group title |
5% Carbogen
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Reporting group description |
Inhalation of 5% Carbogen | ||
Reporting group title |
5% Carbogen
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Reporting group description |
Inhalation of 5% Carbogen | ||
Subject analysis set title |
Carbogen Tolerability
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects that underwent treatment with carbogen.
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End point title |
Tolerated period of carbogen inhalation [1] | ||||||||
End point description |
In line with the feasibility focus, the key primary endpoint for this study was the tolerated period of carbogen inhalation. The protocolised period of inhalation was 120 seconds of inhalation of 5% carbogen.
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End point type |
Primary
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End point timeframe |
End of scheduled inhalation period.
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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: No applicable statistical analyses. The primary objective of the trial was to determine the feasibility of the protocol. As only 6 out of a target of 30 participants were recruited in the designated time period the DMC determined that the trial was not feasible. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Respiratory rate before inhalation | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Immediately prior to inhalation of carbogen
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| No statistical analyses for this end point | |||||||||
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End point title |
Respiratory rate immediately post inhalation | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Immediately after inhalation of carbogen
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| No statistical analyses for this end point | |||||||||
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End point title |
Capilllary pO2 post inhalation | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Immediately post inhalation of carbogen
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| No statistical analyses for this end point | |||||||||
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End point title |
Capilllary pCO2 post inhalation | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Immediately post inhalation of carbogen
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| No statistical analyses for this end point | |||||||||
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End point title |
Blood pH post inhalation | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Post inhalation of carbogen
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were reported from time of consent until 7 days post IMP administration.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
None used | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
5% Carbogen
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Reporting group description |
Inhalation of 5% Carbogen | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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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22 Oct 2012 |
Due to the face mask for administering the IMP being loosely applied to the face, for participant comfort, there was a risk of the carbogen being diluted by room air. Therefore, this amendment proposed to increase the flow rate of carbogen administration to counteract any possible dilution. |
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03 Jan 2013 |
Addition of two research sites. |
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13 Nov 2013 |
Removal of the requirement for participants to remain in hospital for 24h after inhalation as this was seen as burdensome and a reason for nonparticipation in the study by families. The Trial Steering Committee strongly recommended that this requirement be relaxed and follow-up arrangements be more proportionate to risks of the study. Participants allowed home before the 24h observation point were to be followed up by an outpatient review on the first day after inhalation.
In addition the day 7 review was modified to allow it to take place by telephone rather than face to face review. The end of the follow-up period was standardised at seven days, rather than seven days or duration of inpatient stay whichever was the longer. |
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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. | |||
| Recruitment to the trial was extremely difficult and 6 participants were recruited from a target of 30. On the advice of the data monitoring committee, the study was then terminated for lack of feasibility therefore analyses are descriptive only. | |||
