E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Angiotensin – Converting – Enzyme – Inhibitors (ACEi) are used in the treatment of several types of cardiovascular and renal diseases. A known side effect of ACEi are angioedema of the head and neck region. These can lead to severe dyspnoea and the need for intubation and are thought to be bradykinin mediated. Up until now there is no study-evaluated conservative therapeutic concept for the treatment of these patients. |
Das primäre Ziel ist die Prüfung der Wirksamkeit des verabreichten C1-Esterase-Inhibitor im Vergleich zur bisherigen Standardbehandlung bestehend aus einer intravenösen Applikation von 500 mg Soludecortin H (Wirkstoff: Prednisolon-21-hydrogensuccinat, Natriumsalz) und 2 mg Tavegil (Wirkstoff: Clemastinhydrogenfumarat) bei ACE-Hemmer induzierten Angioödemen der oberen Atemschluckstraße. |
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E.1.1.1 | Medical condition in easily understood language |
Patient with induced ACEi Angioedem. |
Patienten mit einem ACEi induziertem Angioödem. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002425 |
E.1.2 | Term | Angioedemas |
E.1.2 | System Organ Class | 100000004870 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective:
To show that Berinert shortens the time to complete resolution of signs and symptoms of acute ACE-induced angioedema of the upper airway tract compared to placebo when given on top standard treatment
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
To compare the time to onset of relief as defined by a at least one point reduction of severity scale of ACE-induced angioedma with Berinert vs placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent to participate in the study and ability to fulfil all study requirements
Male or female patients aged 18 years
Patients with ACE induced angioedema (grade II-III in at least one severity scale) with imminent airway obstruction admitted to an Emergency department
Patient is being treated with ACEi
Patient must have acute angioedema attack caused by ACEi
Treatment should be administered within 10 hours after onset of the angioedema
Patients with angioedema of the head and/or neck (face, lips, cheeks, tongue, soft palate/uvula, pharynx and larynx)
Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country
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E.4 | Principal exclusion criteria |
Diagnosis of angioedema of other genesis: e.g. hereditary angioedema, C1-inhibitor deficiency, allergic oedema, anaphylaxis, insect bite, trauma, abscess, local inflammation,
local tumour, post-operative or post-radiogenic oedema, salivary gland disorders
Participation in a clinical study in the past 30 days
Patients with simultaneous itchiness of skin (acute urticaria)
Patients with a history of angioedema before taking ACEI
History of hypersensitivity to any of the study drugs or medicine with a similar chemical structure.
Pregnancy and/or breastfeeding
Mental retardation of the patient with restriction of general judgment and awareness
History of drug abuse (including alcohol and alcoholic liver disorders)
Potentially unreliable patients
Patients who are not suitable for the study in the opinion of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint:
The primary endpoint is the physician-assessed time to complete resolution of signs and symptoms of the ACE-induced angioedema at lips, tongue, hyopharynx or larynx maintained at least for one hour follow-up time measurement |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary data analysis will be on all patients receiving study medication (ITT). The observed longest resolution times of the most severely affected anatomical location will be taken as the primary endpoint time measure. In an additional sensitivity analysis resolution time measures in patients who require rescue medication will be imputed with the longest resolution time interval observed in the study (worst-case imputation rule). |
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E.5.2 | Secondary end point(s) |
Secondary endpoint:
Time between start of study medication administration and time of onset of relief defined by at least one point reduction of oedema severity score. The severity score of the upper airway obstruction will be assessed by the treating physician using a 4 grade (I-IV) assessment scale that describes the severity at 4 anatomical locations of the upper airway tract (lips, tongue, hyopharynx, and larynx).
Occurrence of adverse events ( serious and unserious), most notably the occurrence of any thrombotic events (e.g. myocardial infarction, venous thrombosis and others) up to 4 weeks after study drug administration. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time between start of study medication administration and time of onset of relief, defined by at least one point reduction of oedema severity scale, will be described by median, quartiles, mean, min and max for both groups. Kaplan-Meier analysis will be performed for the two treatment groups, censoring patients who did not achieve complete restitution and ones who received rescue medication.
The between group difference will be accessed both with the Log-rank and with the Wilcoxon test.
Occurrence of adverse events ( serious and unserious), most notably the occurrence of any thrombotic events (e.g. myocardial infarction, venous thrombosis and others) up to 4 weeks after study drug administration. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end after 52 Patients were included.
It is estimated that all patients can be included within 30 month |
Die Studie wird beendet wenn 52 Patienten eingeschlossen wurden . Es ist geplant, dass innerhalb von 30 Monaten alle Patienten eingeschlossen sind.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |