Clinical Trial Results:
Open, comparative, randomized study on the efficacy, safety and bioavailability of highly concentrated inhaled epinephrine (4 mg L-epinephrine / ml, Infectokrupp® Inhal) versus epinephrine autoinjector application (Fastjekt® Junior) in infants with acute anaphylactic reaction during a food provocation.
TRANCHE - TReatment of ANaphylaxis in CHildren with Epinephrine
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Summary
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EudraCT number |
2014-000097-19 |
Trial protocol |
DE |
Global end of trial date |
31 Dec 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Feb 2026
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First version publication date |
19 Feb 2026
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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 |
TRANCHE
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Charité - Universitätsmedizin Berlin
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Sponsor organisation address |
Charitèplatz 1, Berlin, Germany, 10115
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Public contact |
Prof. Dr. med. Kirsten Beyer, Klinik für Pädiatrie m. S. Pneumologie und Immunologie, Campus Virchow Klinikum, 49 30450659054, kirsten.beyer@charite.de
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Scientific contact |
Prof. Dr. med. Kirsten Beyer, Klinik für Pädiatrie m. S. Pneumologie und Immunologie, Campus Virchow Klinikum, 49 30450659054, kirsten.beyer@charite.de
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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 |
05 Jan 2026
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Dec 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2024
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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 |
Mean change of anaphylaxis symptom scores (ASC, considered weighted symptoms of the organ systems (CASC) and if necessary use of an additional medicinal anaphylaxis therapy, DASC) evaluated from baseline to endpoint after 20 minutes (for the FA (Full-Analysis-) population)
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Protection of trial subjects |
The study was performed in accordance with the ethical principles stated in the Declaration of Helsinki. The study was conducted with agreement with ICG-GCP and other national regulations.
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Background therapy |
Anaphylaxis is a severe, life-threatening allergic reaction that requires immediate medical attention. Epinephrine administration as the most critical treatment for anaphylaxis is usually performed intramuscularly. However, there is strong hesitancy for autoinjector use, especially among caregivers, and a need for effective needle-free options. Pharmacokinetic studies in healthy volunteers indicate that systemic absorption of highly concentrated nebulized inhaled epinephrine is rapid and has a good bioavailability, thus can reach therapeutic levels, but data on affected young children was lacking. This observer-blinded, randomized, controlled clinical trial investigated the effectiveness, safety and bioavailability of highly concentrated inhaled nebulized epinephrine (Infectokrupp® Inhal) vs. epinephrine autoinjector use (Fastjekt® Junior) in young children with acute anaphylactic reaction during an oral food challenge. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Germany: 26
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Worldwide total number of subjects |
26
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EEA total number of subjects |
26
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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) |
5
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Children (2-11 years) |
21
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Adolescents (12-17 years) |
0
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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 study was conducted from August 21,2017 (FPFV) up to December 9, 2024 (LPLV) at one site in Germany. 141 patients were screened, 26 were randomized and analysed. | |||||||||
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Pre-assignment
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Screening details |
Age 1-6 yrs, Anaphylactic reaction requiring treatment in the context of oral food challenges, defined by: At least 2 affected organ systems (skin, gastrointestinal tract, respiratory tract, and/or cardiovascular system) with an anaphylaxis symptom score of at least 5 points, peripheral or central airway obstruction, reduced sys. blood pressure. | |||||||||
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Period 1
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Period 1 title |
Intervention period (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 |
Due to the different forms of administration (inhalation or intramuscular injection), blinding would have required the additional injection or inhalation of a placebo preparation. This was not done due to the age of the children. However, 10 minutes and 20 minutes after the onset of the anaphylactic reaction requiring intervention, an independent medical assessment of the patient was carried out by another investigator who was “blinded” to the treatment group of the respective patient.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Infectokrupp - Inhalation | |||||||||
Arm description |
Treatment by inhalation | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Epinephrine
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Investigational medicinal product code |
E4250
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Other name |
Adrenaline; ATC Code: C01 CA24
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Pharmaceutical forms |
Solution and dispersion for nebuliser dispersion
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Routes of administration |
Inhalation use
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Dosage and administration details |
1-2 ml (4-8 mg Epinephrin). Infectokrupp® Inhal was inhaled continuously for 10 minutes using a fully filled Infectopharm Pocket Nebulizer®. At a nebulization rate of 2:45 min/ml specified by the Infectopharm pocket nebulizer® used, approximately 3.5 ml of Infectokrupp® Inhal is nebulized, which, taking into account the repeat therapy, is within the dosage recommendation range specified in the product information.
The test medication was administered after an anaphylactic reaction requiring immediate treatment was detected during an oral food challenge. The inclusion criteria regarding age and weight were designed to ensure that the recommended dose of adrenaline was administered with the available test preparations.
All patients received standard therapy in the form of (concomitant) intravenous administration of antihistamines (clemastine intravenously (Tavegil®) at a dosage of 0.5 mg for children weighing less than 25 kg and 1.0 mg for children weighing 25 kg or more).
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Arm title
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Fastjekt - Injection | |||||||||
Arm description |
Treatment by intramuscular injection | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Epinephrin
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Investigational medicinal product code |
E4250
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Other name |
Adrenalin, ATC Code: C01 CA24
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection
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Dosage and administration details |
The pediatric dosage for children weighing 7.5–25 kg for emergency allergy treatment was 150 micrograms of epinephrine (adrenaline) injected intramuscularly using an auto-injector "Fastjekt® Junior".
All patients received standard therapy in the form of (concomitant) intravenous administration of antihistamines (clemastine intravenously (Tavegil®) at a dosage of 0.5 mg for children weighing less than 25 kg and 1.0 mg for children weighing 25 kg or more) and systemic glucocorticoid (prednisolone (Decortin®) at a dosage of 5 mg/kg body weight). In cases of clinically relevant blood pressure drop, intravenous administration of volume (20 ml/kg body weight NaCl 0.9%) was possible; in cases of clinically relevant bronchial obstruction, 2 puffs of salbutamol metered dose inhaler via inhalation aid (spacer) were administered.
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Baseline characteristics reporting groups
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Reporting group title |
Infectokrupp - Inhalation
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Reporting group description |
Treatment by inhalation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fastjekt - Injection
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Reporting group description |
Treatment by intramuscular injection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Infectokrupp - Inhalation
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Reporting group description |
Treatment by inhalation | ||
Reporting group title |
Fastjekt - Injection
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Reporting group description |
Treatment by intramuscular injection | ||
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End point title |
change ASC | ||||||||||||||||||
End point description |
Mean change in anaphylaxis symptom score (ASC, weighted to take into account symptoms in the organ systems (CASC) and any necessary additional medical treatment for anaphylaxis (DASC)) from baseline to the endpoint after 10 minutes.
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End point type |
Primary
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End point timeframe |
from Baseline up to 10 minutes after intervention
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Statistical analysis title |
Inhalation vs. Injection Group | ||||||||||||||||||
Statistical analysis description |
The comparison of the mean values of the end-baseline differences between the intramuscular and inhalation groups was exploratory and non-confirmatory
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Comparison groups |
Infectokrupp - Inhalation v Fastjekt - Injection
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||
P-value |
= 0.9161 | ||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
overall trial
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
Inhalation Group
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Reporting group description |
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Reporting group title |
Injektion Group
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Reporting group description |
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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02 Nov 2016 |
The protocol (Version 1.0, dated 01.08.2016) was updated :
- change in case number planning and statistical analysis
- change of schedule and risk management
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25 Oct 2017 |
-protocol update:
- extension of the duration of study
- change of inclusion criteria (update product information for the study preparation PR2 “Fastjekt Junior”) |
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08 Jan 2020 |
update Protocol Version 2.1 (21/11/2019), extension of study duration |
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26 May 2021 |
update protocol V 3.0 (31./03/2021); extension study duration due to the time lost during the coronavirus pandemic, Identification of AE as possible reasons for protocol violations during the study, e.g., shortened inhalation times. |
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28 Jul 2021 |
update SmPC of "FASTJEKT Junior" and update IB of KruppInhal |
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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. | |||
| There were temporary interruptions or reductions in the inhalation time during inhalation. | |||
