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. MedDRA version: 18.1 Level: HLT Classification code 10002425 Term: Angioe
Conditions
Interventions
Product Name: Prednisolon-21-hydrogensuccinat
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Prednisolon-21-hydrogensuccinat
CAS Number: 2920-86-7
Concentration unit: mg milligram(s)
Sponsors
Medizinische Fakultät der Technischen Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 ;Secondary Objective: 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 ;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;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). | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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. | — |
Countries
Germany
Contacts
Public ContactBeate Schossow
Muenchner Studienzentrum
Outcome results
None listed