Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema

Recruiting

• Conditions: Angio-Oedema Caused by Angiotensin-Converting-Enzyme Inhibitor

• Registration Number: NCT04763577
• Lead Sponsor: University Hospital, Grenoble

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-16
• Study First Submitted QC: 2021-02-16
• Study First Posted: 2021-02-21
• Study Start: 2021-10-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-25
• Primary Completion: 2025-10-26
• Study Completion: 2025-10-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 243

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prognostic Value of Bradykinin degradating enzymes	Association between the activity of kinin-degrading enzymes (ECA, APP, DPP4) measured by enzyme methods, expressed in tertiles, and relapse at 6 months.	The primary outcome is to determine the dynamic prognostic value of each of the kinin catabolism enzyme activities, as biomarkers of the risk of relapse at 6 months in patients with BK-AE associated with ACEi.

Trial Locations

Locations (4)

CHRU de Lille _Hôpital Claude-Huriez; 🇫🇷 Lille, France

Chu Grenoble Alpes; 🇫🇷 Grenoble, France

AP-HP _St Antoine; 🇫🇷 Paris, France

CHU de Rouen; 🇫🇷 Rouen, France