Clinical trial NCT04763577: Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema
Official title: Prognostic Value of the Bradykinin-degradating Enzymes Activities on the Relapse Risk of Angiotensin-Converting Enzyme Inhibitors-associated Angioedema
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Angio-Oedema Caused by Angiotensin-Converting-Enzyme Inhibitor
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: University Hospital, Paris
name: University Hospital, Rouen
First posted: 2021-02-21
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Angioedema secondary to Angiotensin Converting Enzyme Inhibitors

Brief summary: Angiotensin-Converting-Enzyme-inhibitors-dependent angioedema (ACEi-AE) is the most frequent form of bradykinin-mediated AE, with an estimated prevalence of 0.1% to 0.7%.

These AE can be explained by the accumulation of bradykinin (BK), a peptide responsible for increase of vascular permeability: ACE inhibitors block ACE, the main inactivation pathway of the BK, thus extending its half-life.

In spite of the the stopping of the drug, systematically performed in the case of ACEi-AE, up to 50% of patients relapsed within 6 months, with maximum risk in the first month after stopping. In addition, the discontinuation of these drugs represents a loss of chance for some patients, without clearly established mastocytic (or histaminic) or bradykinic etiology.

At present there is no method to predict the risk of crisis recurrence in patients who have developed AE-IEC.

The investigators hypothesize that the risk of relapse is associated with a decrease in the activity of BK degradation enzymes (including aminopeptidase P (APP), dipeptidyl peptidase-4 (DPP4), and ECA) that persists at the cessation of IEC.


Eligibility criteria: Inclusion Criteria:

* Men and women at least 18 years old
* Presenting AE secondary to treatment with Angiotensin Conversion Enzyme Inhibitors for less than 15 days, or an isolated AE (without superficial hives), which lasts at least 15 hours, and whose diagnosis is validated by the expert committee,
* Having signed informed and written consent
* And being affiliated with social security

Exclusion Criteria:

* Patient who had one or more AEs prior to IEC
* Hereditary or acquired deficiency of C1 inhibitor
* Subject with known mutation of the F12 or PLG gene Subject in times of exclusion from another research involving the human person type 1 or 2 Persons referred to in sections L1121-5 to L1121-8 of the public health code (pregnant woman, breastfeeding mother, person deprived of liberty, person subject to legal protection) subject that cannot be contacted in an emergency situation

Primary outcomes:
measure: Prognostic Value of Bradykinin degradating enzymes
timeFrame: Association between the activity of kinin-degrading enzymes (ECA, APP, DPP4) measured by enzyme methods, expressed in tertiles, and relapse at 6 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Chu Grenoble Alpes
city: Lille
country: France
facility: CHRU de Lille _Hôpital Claude-Huriez
city: Paris
country: France
facility: AP-HP _St Antoine
city: Rouen
country: France
facility: CHU de Rouen
Study officials:
affiliation: University Hospital, Grenoble
name: Federica DEFENDI
role: PRINCIPAL_INVESTIGATOR
References: