Clinical Trial Results:
Etude de la dose-réponse au bronchodilatateur puis recherche de dose du bronchodilatateur par la technique de l'interruption du débit chez l'enfant siffleur âgé de 2,5 à 6 ans - Etude DORESI.
|
Summary
|
|
EudraCT number |
2011-002261-38 |
Trial protocol |
FR |
Global end of trial date |
23 Jan 2014
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
21 Sep 2023
|
First version publication date |
21 Sep 2023
|
Other versions |
|
Summary report(s) |
Article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
P100504
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01470755 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Assistance Publique – Hôpitaux de Paris (AP-HP)
|
||
Sponsor organisation address |
1, avenue Claude Vellefaux, Paris, France, 75010
|
||
Public contact |
Dr BEYDON Nicole, Assistance Publique – Hôpitaux de Paris, nicole.beydon@aphp.fr
|
||
Scientific contact |
Dr BEYDON Nicole, Assistance Publique – Hôpitaux de Paris, nicole.beydon@aphp.fr
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
06 Feb 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
23 Jan 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
23 Jan 2014
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Estimer la relation dose-effet du bronchodilatateur chez le jeune enfant siffleur par la technique de l'interruption du débit aérien.
|
||
Protection of trial subjects |
Children recruited only with their consent and with their parents consents.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jan 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 106
|
||
Worldwide total number of subjects |
106
|
||
EEA total number of subjects |
106
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
106
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||||
Recruitment details |
Start of recruitment : 25/01/2012 End of recruitment : 23/01/2014 recruitment centers : Hôpital Armand Trousseau – Paris, Hôpital Robert Debré – Paris, Hôpital Arnaud de Villeneuve - Montpellier | ||||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||||
Screening details |
Any patient aged 2 years 6 months and 6 years 11 months referred for a pulmonary function test with bronchodilator test, because of recurrent wheezing on at least 3 occasions in the past year. Absence of BD intake in the 12 hours before the examination. Parents who gave signed consent for the study | ||||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||||
Period 1 title |
Inclusion/randomization (overall period)
|
||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||
Blinding implementation details |
The children included will receive 2 successive doses of bronchodilator (BD) at 30 minutes interval, with a Rint measurement between 20 and 30 minutes after each dose. Two doses per child will be tested according to 4 designs that will be randomized. These doses will be evaluated blind to the person measuring the Rint.
|
||||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||
|
Arm title
|
400 µg Salbutamol (100+300) | ||||||||||||||||||||||||||||||
Arm description |
Rint was measured at baseline, and after random assignment to a first dose (100 μg) and a second dose (cumulative dose: 400) | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Salbutamol
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
Ventoline
|
||||||||||||||||||||||||||||||
Pharmaceutical forms |
Inhalation solution
|
||||||||||||||||||||||||||||||
Routes of administration |
Inhalation use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
|
||||||||||||||||||||||||||||||
|
Arm title
|
600 µg Salbutamol (100+500) | ||||||||||||||||||||||||||||||
Arm description |
Rint was measured at baseline, and after random assignment to a first dose (100 μg) and a second dose (cumulative dose: 600) | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Salbutamol
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
Ventoline
|
||||||||||||||||||||||||||||||
Pharmaceutical forms |
Oral suspension in pre-filled oral applicator
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
|
||||||||||||||||||||||||||||||
|
Arm title
|
800 µg Salbutamol | ||||||||||||||||||||||||||||||
Arm description |
Rint was measured at baseline, and after random assignment to a first dose (200 μg) and a second dose (cumulative dose: 800) | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Salbutamol
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
Ventoline
|
||||||||||||||||||||||||||||||
Pharmaceutical forms |
Oral suspension in pre-filled oral applicator
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
|
||||||||||||||||||||||||||||||
|
Arm title
|
400 µg Salbutamol | ||||||||||||||||||||||||||||||
Arm description |
Rint was measured at baseline, and after random assignment to a first dose (200 μg) and a second dose (cumulative dose: 400) | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Salbutamol
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
Ventoline
|
||||||||||||||||||||||||||||||
Pharmaceutical forms |
Oral suspension in pre-filled oral applicator
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
The dosage schedules − first and second doses of salbutamol received 30 min apart − were as follows: 100 + 300, 100 + 500, 200 + 200, and 200 + 600 μg (Figure 1), delivered via a new valve-holding chamber (Vortex®, Pari, Starnberg, Germany). At baseline and 30 min after each dose, pulse oximetry (oxygen saturation [SpO2] and heart rate) and Rint measurements during expiration (MicroRint, Micro Medical Ltd,
Rochester, UK, or SpiroDyn’R, Dyn’R Ltd, Aix-en-Provence, France) were recorded by an investigator blinded to the doses received by the child.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Inclusion/randomization
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Method
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Rint was measured at baseline, and after random assignment to a first dose (100
or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
Data were analyzed using mixed modeling approach with an inhibitory maximal effect
(Imax) model, to account for a sparse sampling design. Simulations were performed to
predict the percentage of children with significant Rint reversibility at several doses.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
400 µg Salbutamol (100+300)
|
||
Reporting group description |
Rint was measured at baseline, and after random assignment to a first dose (100 μg) and a second dose (cumulative dose: 400) | ||
Reporting group title |
600 µg Salbutamol (100+500)
|
||
Reporting group description |
Rint was measured at baseline, and after random assignment to a first dose (100 μg) and a second dose (cumulative dose: 600) | ||
Reporting group title |
800 µg Salbutamol
|
||
Reporting group description |
Rint was measured at baseline, and after random assignment to a first dose (200 μg) and a second dose (cumulative dose: 800) | ||
Reporting group title |
400 µg Salbutamol
|
||
Reporting group description |
Rint was measured at baseline, and after random assignment to a first dose (200 μg) and a second dose (cumulative dose: 400) | ||
Subject analysis set title |
Method
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Rint was measured at baseline, and after random assignment to a first dose (100
or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
Data were analyzed using mixed modeling approach with an inhibitory maximal effect
(Imax) model, to account for a sparse sampling design. Simulations were performed to
predict the percentage of children with significant Rint reversibility at several doses.
|
||
|
|||||||||||||||||||||||||
End point title |
Rint reversibility | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Primary analysis | ||||||||||||||||||||||||
Statistical analysis description |
Repeated Rint measurements were simultaneously analyzed in all patients by mixed effect modeling approach which can
compensate for the lack of individual information by borrowing strength from the whole data, and therefore, allow for precise
parameter estimation even with sparse sampling design.Each parameter was composed of two parts: a fixed effect which
represented the median value of this parameter in the study population;a random effect which accounted for the interindividual variability
|
||||||||||||||||||||||||
Comparison groups |
400 µg Salbutamol (100+300) v 600 µg Salbutamol (100+500) v 800 µg Salbutamol v 400 µg Salbutamol
|
||||||||||||||||||||||||
Number of subjects included in analysis |
99
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [1] | ||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
| Notes [1] - dose-response |
|||||||||||||||||||||||||
|
|||
|
Adverse events information [1]
|
|||
Timeframe for reporting adverse events |
During all the study period (25/01/2012 - 23/01/2014)
|
||
Adverse event reporting additional description |
No Adverse event has been reported to the sponsor during the study duration.
|
||
Assessment type |
Systematic | ||
|
Dictionary used for adverse event reporting
|
|||
Dictionary name |
Internal document | ||
Dictionary version |
1
|
||
| Frequency threshold for reporting non-serious adverse events: 5% | |||
| 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: There are no non-serious adverse events reported in this study |
|||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
25 May 2012 |
Addition of beta2-adrenergic receptor genotyping study as a source of variation in bronchodilator dose-response |
||
21 Mar 2013 |
Participation of the Physiology-Functional Explorations Department of the Robert Debré Hospital in Paris in the genetic study complementary to the DORESI study |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
