Trial document




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  DRKS00011881

Trial Description

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Title

Open label, comparative, randomized trial of the efficacy, safety and bioavailability of highly concentrated inhalative epinephrine (4 mg L-Epinephrin/ml, Infectokrupp® Inhal) versus Epinephrin-Autoinjektor-Anwendung (Fastjekt® Junior) in infants with acute anaphylactic reaction in the course of a food challenge

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Trial Acronym

TRANCHE - TReatment of ANaphylaxis in CHildren
with Epinephrine

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URL of the Trial

https://www.charite-ppi.de/forschung/klinische_studien/

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Brief Summary in Lay Language

Food allergies occur especially in infants. Anaphylactic (severe allergic) reactions at accidental ingestion or within a clinically indicated oral food challenge are thereby not always avoidable. So far for anaphylactic reactions intramuscular adrenaline injections (injected in the muscle), for example via adrenaline autoinjectors, are used. An inhalative administration of adrenaline would be a preferable alternative. Inhalative adrenaline is routinely applied at pseudocroup which occurs especially in infants but is also approved for respiratory distress of allergic origin, however not for the therapy of anaphylaxis. However new data shows, that highly concentrated nebulized adrenaline (Infectokrupp® Inhal), which is inhaled continuously via liquid inhalation, is absorbed systemically in sufficient amounts and thus could also be effective in anaphylaxis. Since the studies, to which the data refers, were conducted in healthy adults though, the transfer to children with acute anaphylactic reaction remains unsettled. In the course of this clinical study inhalative adrenaline (epinephrine) (4 mg L-Epinephrine/ml, Infectokrupp® Inhal) is compared to the use of adrenaline autoinjector (Fastjekt® Junior). Which of these therapies the child will receive in case of an anaphylactic reaction in the course of a clinically indicated oral food challenge during participation, is decided by a preassigned random process similar to tossing a coin; this is called randomization. The chance of receiving one of the two preparations is 50 %. So, the child receives adrenaline in any case. Both utilized preparations, Infectokrupp® Inhal and Fastjekt® Junior, are available on the market and are also approved for use in children. By performing the designated clinical study, we expect to clarify whether through liquid inhalation of adrenaline with Infectokrupp ® Inhal an equivalent relief of symptoms of anaphylaxis can be reached as through the intramuscular application.

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Brief Summary in Scientific Language

Food allergies occur especially in infants. Anaphylactic reactions at accidental ingestion or within a clinically indicated oral food challenge are thereby not always avoidable. So far for anaphylactic reactions intramuscular adrenaline injections, for example via adrenaline autoinjectors, are used. An inhalative administration of adrenaline would be a preferable alternative. Inhalative adrenaline is routinely applied at pseudocroup which occurs especially in infants but is also approved for respiratory distress of allergic origin, however not for the therapy of anaphylaxis. Up to now it was assumed that, based on bioavailability data of adrenaline metered-dose inhalers, the systemic effect of the inhalative adrenaline is possibly not sufficient to treat an anaphylaxis. However new data shows, that highly concentrated nebulized adrenaline (Infectokrupp® Inhal), which is inhaled continuously via liquid inhalation, is absorbed systemically in sufficient amounts and thus could also be effective in anaphylaxis. Since the studies, to which the data refers, were conducted in healthy adults though, the transfer to children with acute anaphylactic reaction is questionable.In the course of this clinical study inhalative adrenaline (epinephrine) (4 mg L-Epinephrine/ml, Infectokrupp® Inhal) is compared to the use of adrenaline autoinjector (Fastjekt® Junior) in a randomized manner (1:1).So, the child receives adrenaline in any case. Both utilized preparations, Infectokrupp® Inhal and Fastjekt® Junior, are available on the market and are also approved for use in children. By performing the designated clinical study, we expect to clarify whether through liquid inhalation of adrenaline with Infectokrupp ® Inhal an equivalent relief of symptoms of anaphylaxis can be reached as through the intramuscular application.

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Organizational Data

  •   DRKS00011881
  •   2017/06/29
  •   [---]*
  •   yes
  •   Approved
  •   16/0201-EK 12, Ethik-Kommission des Landes Berlin
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Secondary IDs

  •   U1111-1197-9721 
  •   2014-000097-19 
  •   4041183 
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Health Condition or Problem studied

  •   T78.0 -  Anaphylactic shock due to adverse food reaction
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Interventions/Observational Groups

  •   Epinephrine, FASTJEKT® Junior,
    intramuscular
    150 µg
    solution for injection via autoinjektor
  •   Epinephrin , INFECTOKRUPP® inhal,
    inhalative
    4 mg/ml
    solution for inhalation for nebuliser
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   II
  •   Yes
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Primary Outcome

Primary outcome is the mean change of the Anaphylaxis-Symptom-Score (ASC, takes into account weighted symptoms in the organ systems (CASC) as well as if necessary the use of an additional medicinal anaphylaxis-therapy, DASC, see below) from baseline until the time after 10 minutes (by the “First-Investigator”).

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Secondary Outcome

Epinephrine plasma levels 10 minutes after the start of application of the investigational product and change in relation to baseline-measurements at t1a; ASC and change to Baseline (t1b) at all recording times (5, 10, 15, 20, 25, 30, 40, 50, 60 min.); ASC single score values, sum of the clinical score values (CASC), sum of the additional anaphylaxis therapy score values (DASC) and change in relation to baseline (t1b) at all recording times; use of additional medical therapies for the treatment of the anaphylactic reaction; AEs, SAEs and side effects.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2018/03/19
  •   40
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   1   Years
  •   6   Years
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Additional Inclusion Criteria

„Run-in“-Phase:
• written informed consent of the parents to study participation
• age: 1 to 6 years of age
• Weight 7.5 to 30 kg
• planned inpatient admission in the context of a medically indicated oral food challenge

“Treatment”-Phase:
• treatment-requiring anaphylactic reaction in the course of the oral food challenges, defined as:
(1.) at least two affected organ systems (skin, gastrointestinal tract, airways, and/or heart/circulation) with an anaphylaxis symptom score of at least 5 points or
(2.) peripheral or central airway obstruction or
(3.) drop in blood pressure (reduced systolic blood pressure 70 mm Hg plus 2 x age in years or drop in blood pressure: >30% drop of the systolic blood pressure)

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Exclusion Criteria

- acute febrile infection
- known clinically relevant cardiac and circulatory disorders such as angina pectoris, obstructive cardiomyopathy, cardiac arrhythmias, coronary heart vessel diseases, diseases of the heart muscle, sclerotic vascular changes, cor pulmonale or atherosclerosis and clinically relevant hypertension
- known clinically relevant diabetes
- known hypercalcemia or hypokalemia
- known hyperthyroidism
- known phaeochromocytoma
- known severe renal impairment or
- bladder voiding disorders with residual urine formation
- known angle-closure glaucoma
- known other serious diseases which, according to the investigator’s judgement, hinder a participation
- known presence of other contraindications according to the medicinal product’s professional information of the investigetional products used (Infectokrupp® Inhal, Fastjekt® Junior), in particular the use of a contraindicated concomitant medication (see below)
- anamnestically known hypersensitivity reactions to components of one of the investigational products used, in particular sodium metabisulfite
- Prior participation in this study
- Participation in a clinical trial in the last 30 days
- inability of the parents to understand the study instructions; obvious unreliability or lack of cooperation of the parents
- use/intake of any of the following contraindicated concomitant medications or therapies:
- beta-blocker or alpha-receptor blocker
- digitalis glycosides, quinidines, halothane or cyclopropane
- levodopa, parasympatholytics (e.g. atropine)
- sympathomimetics, e.g. orciprenaline
- tri- and tetracyclic antidepressants
- monoamine oxidase inhibitors
- guanethidine, L-thyroxine
- oxytocin, ornipressin, carbazochrom
- insuline, antidiabetic drugs
- reserpine, mecamylamine
- certain antihistamines: diphenhydramine, chlorphenamine
- preparations which lead to potassium loss, e.g. potassium withdrawing diuretics, aminophylline or theophylline
- alcohol-containing preparations
- antihistamines or leukotriene receptor antagonists during the last 72 hours
- long-acting beta-2-mimetics or theophylline during the last 48 hours
- lack of willingness to store and transfer pseudonymized disease data within the limits of the clinical trial
- Accommodation in an institution by judicial or administrative order
- Patients and parents who are dependent on the investigator, the sponsor or the investigational site

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Addresses

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    • Charité Campus Virchow-Klinikum
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité Campus Virchow-KlinikumKlinik für Pädiatrie m.S. Pneumologie und Immunologie
    • Ms.  Prof. Dr. med.  Kirsten  Beyer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Kinderallergologisches Studienzentrum
    • Ms.  Susanne  Paschke-Goossens 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • InfectoPharm Arzneimittel
    • Von-Humboldt-Str. 1
    • 64646  Heppenheim
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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